WO1993025544A1 - Process for producing amine-boranes - Google Patents
Process for producing amine-boranes Download PDFInfo
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- WO1993025544A1 WO1993025544A1 PCT/US1992/005141 US9205141W WO9325544A1 WO 1993025544 A1 WO1993025544 A1 WO 1993025544A1 US 9205141 W US9205141 W US 9205141W WO 9325544 A1 WO9325544 A1 WO 9325544A1
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- WO
- WIPO (PCT)
- Prior art keywords
- pyridine
- borane
- amine
- boranes
- product
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- 229910000085 borane Inorganic materials 0.000 title abstract description 12
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000011541 reaction mixture Substances 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 7
- 229960005332 zileuton Drugs 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000013019 agitation Methods 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000526 short-path distillation Methods 0.000 description 2
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 description 1
- 102000011730 Arachidonate 12-Lipoxygenase Human genes 0.000 description 1
- 108010076676 Arachidonate 12-lipoxygenase Proteins 0.000 description 1
- 102000009515 Arachidonate 15-Lipoxygenase Human genes 0.000 description 1
- 108010048907 Arachidonate 15-lipoxygenase Proteins 0.000 description 1
- YPKATNMCYFSXKB-UHFFFAOYSA-O CC(c1cc2ccccc2[s]1)N[OH2+] Chemical compound CC(c1cc2ccccc2[s]1)N[OH2+] YPKATNMCYFSXKB-UHFFFAOYSA-O 0.000 description 1
- IKJPIIYMCPNDCT-SERMCNLOSA-N C[C@]1(/C(/C)=N/O)Sc2ccccc2C1 Chemical compound C[C@]1(/C(/C)=N/O)Sc2ccccc2C1 IKJPIIYMCPNDCT-SERMCNLOSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000004653 carbonic acids Chemical class 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- -1 di trialkyl amine Chemical class 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical class [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007772 electroless plating Methods 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/58—Radicals substituted by nitrogen atoms
Definitions
- This invention relates to the production amine- boranes. More particularly, the invention relates to the product of a stable, pure, pyridine-borane substantially free of color.
- Aromatic, aliphatic, alicyclic and aromatic heterocyclic amine-boranes are useful as reducing agents for various substrates, in reductive amination reactions, in the hydroboration of alkenes and alkynes, in procedures for the electroless plating of metals and in the synthesis of ceramic and preceramic materials.
- pyridine-borane is a key reagent in the synthesis of zileuton [N-l(l-benzo [b] thien-2-ylethyl) -N-hydroxyurea]
- Zileuton is a 5-lipoxygenase inhibitor devoid of cyclooxygenase and 12- and 15-lipoxygenase inhibitory activity. See, e.g., DN&P 4 (1) ;46 et. seg. Pyridine-borane is used in the penultimate step of zileuton synthesis as shown by the following Equation I:
- This invention provides a method for the preparation of highly pure stable amine-boranes.
- a specific embodiment of the invention provides pure, stable pyridine-borane which is substantially free of color and hence "water white”.
- pyridine is reacted with an alkali metal borohydride in a weakly acidic aqueous medium to produce a pyridine-borane containing reaction mixture.
- the pyridine-borane product is then stabilized with a strong base, e.g., aqueous sodium or potassium hydroxide.
- the pyridine-borane product is azeoptropically dried.
- Purity, as determined by iodometric titration is preferably 92-96%. Yield, corrected for purity, is approximately 70-90%. DESCRIPTION OF THE FIGURE
- Figure 1 is a schematic illustration of one form of apparatus which may be used to practice the invention.
- the invention entails a combination of steps which yield stable pure substantially water white amine-boranes including pyridine-borane.
- an amine such as di trialkyl amine, preferably pyridine is reacted with an alkali metal borohydride in a weakly acidic aqueous medium. Hydrogen evolved by the reaction may be released through an oil bubbler or otherwise disposed of.
- the reaction vessel is precharged with pyridine.
- the alkali metal borohydride is added followed by aqueous weak acid.
- the temperature of the reaction mixture is controlled to maximum of about 30°C to about 35°C.
- Evolved hydrogen is released from the system, e.g., through an oil bubbler.
- the aqueous acid is preferably added over a period of about 2.5 to 3 hours.
- An aqueous solution of a strong, preferably inorganic base is added to increase the pH of the reaction mixture and neutralize the excess acid.
- the neutralized reaction mixture separates into an upper layer containing the pyridine-borane product and a lower aqueous layer which is discarded.
- the pyridine-borane product layer is preferably stabilized by addition of and agitation with an aqueous solution of a strong base.
- the resulting lower aqueous layer is separated and discarded, excess pyridine is removed from the amine-borane product layer, preferably by short path distillation under reduced pressure to a final pressure of less than 5 mm Hg and a maximum pot temperature of about 50°C to about 60°C, i.e., 50°C to 60°C, plus or minus 5°C.
- Final purity of the pyridine-borane product may be determined by iodometric titration. Final purities when so determined are usually 90 to 96%. Final yields corrected for purity are approximately 80%.
- the weak acid utilized in the invention preferably has a pKa greater than 2.2.
- Acetic, formic, citric, and carbonic acids are appropriate.
- Aqueous sodium bicarbonate acid, mono and disodium phosphates may be used.
- Strong protic acids which have a pKa less than 2.2 in water, e.g., phosphoric, hydrochloric and sulfuric acids, can be used but provide reduced yields of lower quality pyridine-borane product.
- Water and the weak acid are preferably added concurrently to the reactor containing pyridine and borohydride reactants.
- glacial acetic acid and water are concurrently added to the reaction mixture.
- the proportions of these reactants may range from about 0.5 to 2.5 but preferably is about 1:2.
- Preferred alkali metal hydroxides are NaOH, KOH and LIOH, utilized in about 40% to 60% aqueous solution.
- the method of the invention entails the formation of an amine-borane, in particular, pyridine-borane, preferably in a weakly acid aqueous medium.
- the amine-borane reaction product is stabilized by agitation or the like with a strong base and then azeotropically dried.
- Mono, di, and trialkyl amine-boranes are produced in like manner.
- This exemplification describes the invention as applied to produce pure, stable, substantially water white, pyridine-borane in a yield, corrected for purity, of approximately 80%.
- the 2000 ml 3-neck flask 1 is fitted with Claisen adapters which provide two addition funnels 2 (a 125 ml funnel for glacial acetic acid) and 3 (a 250 ml funnel for water) .
- a condensor 4 and a thermometer 5 are accommodated by the flask as shown in the Figure.
- a mechanical stirrer 6 is provided in the flask.
- the flask 1 is charged with 145.0 g (1.83 mol) of pyridine. With cooling sodium borohydride (56.7 gr-1.50 mol) is added. The temperature of the reaction mixture is then adjusted at 20-25°C.
- Funnel 2 is charged with glacial acetic acid (95.0 g, 1.58 mol).
- Funnel 3 is charged with water (190 g, 10.6 mol) .
- the pyridine-borane layer is stirred for about one hour in the presence of 4 grams of solid NaOH and then filtered. Excess pyridine is removed by short path distillation under reduced pressure to a final pressure of less than 5 mm Hg and a maximum pot temperature of 55°C.
- the pyridine-borane product is used to produce zileuton pursuant to Equation I.
- the zileuton product is substantially free of colored contaminants.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
A method for producing amine-boranes, specifically pyridine-borane which is highly stable and of good color is described.
Description
PROCESS FOR PRODUCING AMINE-BORANES
FIELD OF INVENTION
This invention relates to the production amine- boranes. More particularly, the invention relates to the product of a stable, pure, pyridine-borane substantially free of color.
BACKGROUND OF THE INVENTION
Aromatic, aliphatic, alicyclic and aromatic heterocyclic amine-boranes are useful as reducing agents for various substrates, in reductive amination reactions, in the hydroboration of alkenes and alkynes, in procedures for the electroless plating of metals and in the synthesis of ceramic and preceramic materials.
Of particular importance in the context of this invention is the fact that pyridine-borane is a key reagent in the synthesis of zileuton [N-l(l-benzo [b] thien-2-ylethyl) -N-hydroxyurea]
Zileuton is a 5-lipoxygenase inhibitor devoid of cyclooxygenase and 12- and 15-lipoxygenase inhibitory activity. See, e.g., DN&P 4 (1) ;46 et. seg. Pyridine-borane is used in the penultimate step of zileuton synthesis as shown by the following Equation I:
Zileuton
EQUATION I
The various known methods for the production of pyridine-borane are each attended by disadvantages. Pyridine-borane produced by passage of diborane through pyridine is frequently contaminated with by-products and hence unstable and of poor color. Pyridine-borane synthesis in non-aqueous systems, which require large solvent volumes with consequent low through-put also yields an unstable and impure product. Facilitation of the reactions required to produce pyridine-borane by electrolytic or mechanical agitation presents engineering difficulties and safety concerns.
The problems which attend these prior art methods create a need for a new synthesis which yields stable pyridine-borane and other amine-boranes of improved stability and color suitable for use in the synthesis of drugs such as zileuton.
SUMMARY OF THE INVENTION
This invention provides a method for the preparation of highly pure stable amine-boranes. A specific embodiment of the invention provides pure, stable pyridine-borane which is substantially free of color and hence "water white". Pursuant to the invention, pyridine is reacted with an alkali metal borohydride in a weakly acidic aqueous medium to produce a pyridine-borane containing reaction mixture. The pyridine-borane product is then stabilized with a strong base, e.g., aqueous sodium or potassium hydroxide. The pyridine-borane product is azeoptropically dried. Purity, as determined by iodometric titration, is preferably 92-96%. Yield, corrected for purity, is approximately 70-90%. DESCRIPTION OF THE FIGURE
Figure 1 is a schematic illustration of one form of apparatus which may be used to practice the invention.
DETAILED DESCRIPTION OF THE INVENTION
The invention entails a combination of steps which yield stable pure substantially water white amine-boranes including pyridine-borane.
Pursuant to the invention, an amine such as di trialkyl amine, preferably pyridine is reacted with an alkali metal borohydride in a weakly acidic aqueous medium. Hydrogen evolved by the reaction may be released through an oil bubbler or otherwise disposed of.
In the preferred practice of the invention, the reaction vessel is precharged with pyridine. The alkali metal borohydride is added followed by aqueous weak acid. The temperature of the reaction mixture is controlled to maximum of about 30°C to about 35°C. Evolved hydrogen is released from the system, e.g., through an oil bubbler. The aqueous acid is preferably added over a period of about 2.5 to 3 hours.
An aqueous solution of a strong, preferably inorganic base is added to increase the pH of the reaction mixture and neutralize the excess acid. The neutralized reaction mixture separates into an upper layer containing the pyridine-borane product and a lower aqueous layer which is discarded.
The pyridine-borane product layer is preferably stabilized by addition of and agitation with an aqueous solution of a strong base. The resulting lower aqueous layer is separated and discarded, excess pyridine is removed from the amine-borane product layer, preferably by short path distillation under reduced pressure to a final pressure of less than 5 mm Hg and a maximum pot temperature of about 50°C to about 60°C, i.e., 50°C to 60°C, plus or minus 5°C.
Final purity of the pyridine-borane product may be determined by iodometric titration. Final purities when so determined are usually 90 to 96%. Final yields corrected for purity are approximately 80%.
The weak acid utilized in the invention preferably has a pKa greater than 2.2. Acetic, formic, citric, and carbonic acids are appropriate. Aqueous sodium bicarbonate acid, mono and disodium phosphates may be used. Strong protic acids which have a pKa less than 2.2 in water, e.g., phosphoric, hydrochloric and sulfuric acids, can be used but provide reduced yields of lower quality pyridine-borane product.
Water and the weak acid are preferably added concurrently to the reactor containing pyridine and borohydride reactants. In the preferred practice of the invention, glacial acetic acid and water are concurrently added to the reaction mixture. The
proportions of these reactants may range from about 0.5 to 2.5 but preferably is about 1:2.
Preferred alkali metal hydroxides are NaOH, KOH and LIOH, utilized in about 40% to 60% aqueous solution.
In general, the method of the invention entails the formation of an amine-borane, in particular, pyridine-borane, preferably in a weakly acid aqueous medium. The amine-borane reaction product is stabilized by agitation or the like with a strong base and then azeotropically dried. Mono, di, and trialkyl amine-boranes are produced in like manner. EXEMPLIFICATION OF THE INVENTION
This exemplification describes the invention as applied to produce pure, stable, substantially water white, pyridine-borane in a yield, corrected for purity, of approximately 80%.
Referring to Figure 1, the 2000 ml 3-neck flask 1 is fitted with Claisen adapters which provide two addition funnels 2 (a 125 ml funnel for glacial acetic acid) and 3 (a 250 ml funnel for water) . A condensor 4 and a thermometer 5 are accommodated by the flask as shown in the Figure. A mechanical stirrer 6 is provided in the flask.
The flask 1 is charged with 145.0 g (1.83 mol) of pyridine. With cooling sodium borohydride (56.7 gr-1.50 mol) is added. The temperature of the reaction mixture is then adjusted at 20-25°C.
Funnel 2 is charged with glacial acetic acid (95.0 g, 1.58 mol). Funnel 3 is charged with water (190 g, 10.6 mol) .
Ten (10) ml of water is added to the reaction mixture from funnel 2 over a time period of 1 to 2 minutes. Within two (2) minutes simultaneous addition of acetic acid and water directly into the
reaction mixture is started. The volume ratio of acetic acid:water added is initially about 1:3 and is increased gradually to 1.5 over one hour. This 1.5 ratio is maintained throughout the remaining acetic acid and water addition period of from about 2.5 to 3 hours. During the addition of acetic acid and water, the temperature of the reaction mixture rises from 20-25°C to 30-35°C. Cooling is applied as necessary to maintain the temperature at about 30°-35°C. Hydrogen evolved during the reaction exits from the flask 1 by condensor 4 and is released through an oil bubbler.
About twenty minutes after completion of the water:acetic acid addition, 9.0 g of 50% aqueous NaOH is added to the reaction mixture. About ten (10) minutes thereafter, water (80 g) is added. Thereafter the contents of the flask 1 are transferred to a 1-liter separatory funnel for about 15 to 30 minutes. Thereafter the lower aqueous layer is separated and discarded.
Forty (40) grams of 50% aqueous NaOH was added with agitation to the pyridine-borane containing upper layer. The mixture forms an upper, pyridine- borane layer and a lower aqueous layer which is separated and discarded.
The pyridine-borane layer is stirred for about one hour in the presence of 4 grams of solid NaOH and then filtered. Excess pyridine is removed by short path distillation under reduced pressure to a final pressure of less than 5 mm Hg and a maximum pot temperature of 55°C.
Final purity of the substantially water white product was determined to be 92-96% by iodometric titration. The iodometric titration was carried out by the method described in Jensen, E., et al., Anal. Chem. 2^:1843 (1952).
Yield, corrected for purity, was approximately 80% based on the sodium borohydride reactant.
The pyridine-borane product is used to produce zileuton pursuant to Equation I. The zileuton product is substantially free of colored contaminants.
Claims
1. A method for producing pyridine-borane which comprises:
(i) charging a reaction vessel with pyridine;
(ii) adding an alkali metal borohydride to said pyridine contained in said reaction vessel;
(iii) thereafter concurrently adding a weak acid and water to said reaction vessel in an amount and for a time sufficient to produce the pyridine-borane;
(iv) thereafter adding aqueous alkali metal hydroxide to neutralize the reaction mixture produced by step (iii) ;
(v) separating said pyridine-borane product from said reaction mixture.
2. A method as defined by claim 1 in which said amine is pyridine and in which said alkali metal borohydride is sodium borohydride.
3. A method as defined by claim 1 further comprising step (iv) reacting said pyridine-borane product of step (v) with
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP9292914975A EP0604438A4 (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes. |
| US08/800,384 USRE36115E (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
| PCT/US1992/005141 WO1993025544A1 (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
| CA002115988A CA2115988E (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
| EP97200036A EP0770617A1 (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
| JP6501426A JP2594774B2 (en) | 1992-06-18 | 1992-06-18 | Method for producing amine-borane |
| US08/196,254 US5516909A (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1992/005141 WO1993025544A1 (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
| CA002115988A CA2115988E (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
| EP97200036A EP0770617A1 (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993025544A1 true WO1993025544A1 (en) | 1993-12-23 |
Family
ID=27169707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1992/005141 WO1993025544A1 (en) | 1992-06-18 | 1992-06-18 | Process for producing amine-boranes |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1993025544A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL9500553A (en) * | 1994-04-06 | 1995-11-01 | Bayer Ag | Process for the preparation of dimethylamine borane. |
| WO1999021828A1 (en) * | 1997-09-25 | 1999-05-06 | Abbott Laboratories | Synthesis and isolation of n-(aryl or heteroaryl)-alkyl-n-hydroxyurea |
| EP0894801A3 (en) * | 1997-08-02 | 1999-06-09 | Bayer Ag | Water soluble substituted pyridine boranes |
| US6080874A (en) * | 1997-09-25 | 2000-06-27 | Abbott Laboratories | Synthesis and isolation of N-(aryl or heteroaryl)-alkyl-N-hydroxyurea |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5036067A (en) * | 1990-03-14 | 1991-07-30 | Merck & Co., Inc. | Dibenzoheterocyclic hydroxamic acids and hydroxy ureas as inhibitors of 5-lipoxygenase |
-
1992
- 1992-06-18 WO PCT/US1992/005141 patent/WO1993025544A1/en not_active Application Discontinuation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5036067A (en) * | 1990-03-14 | 1991-07-30 | Merck & Co., Inc. | Dibenzoheterocyclic hydroxamic acids and hydroxy ureas as inhibitors of 5-lipoxygenase |
Non-Patent Citations (3)
| Title |
|---|
| JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 20 March 1955, Vol. 77, No. 6, M. TAYLOR et al., "A Convenient Preparation of Pyridine-Borane", pp. 1506-1507. * |
| JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, February 1942, Vol. 64, H.C. BROWN et al., "Studies in Stereochemistry. I. Steric Strains as a Factor in the Relative Stability of Some Coordination Compounds of Boron", pp. 325-329. * |
| See also references of EP0604438A4 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL9500553A (en) * | 1994-04-06 | 1995-11-01 | Bayer Ag | Process for the preparation of dimethylamine borane. |
| EP0894801A3 (en) * | 1997-08-02 | 1999-06-09 | Bayer Ag | Water soluble substituted pyridine boranes |
| WO1999021828A1 (en) * | 1997-09-25 | 1999-05-06 | Abbott Laboratories | Synthesis and isolation of n-(aryl or heteroaryl)-alkyl-n-hydroxyurea |
| US6080874A (en) * | 1997-09-25 | 2000-06-27 | Abbott Laboratories | Synthesis and isolation of N-(aryl or heteroaryl)-alkyl-N-hydroxyurea |
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