GB1261648A - PROCESS FOR MAKING CRYSTALLINE ALKALI METAL SALTS OF alpha-CARBOXYBENZYL-PENICILLIN - Google Patents
PROCESS FOR MAKING CRYSTALLINE ALKALI METAL SALTS OF alpha-CARBOXYBENZYL-PENICILLINInfo
- Publication number
- GB1261648A GB1261648A GB08574/69A GB1857469A GB1261648A GB 1261648 A GB1261648 A GB 1261648A GB 08574/69 A GB08574/69 A GB 08574/69A GB 1857469 A GB1857469 A GB 1857469A GB 1261648 A GB1261648 A GB 1261648A
- Authority
- GB
- United Kingdom
- Prior art keywords
- alkali metal
- prepared
- acid
- water
- metal salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 229910052783 alkali metal Inorganic materials 0.000 title abstract 12
- 229960003669 carbenicillin Drugs 0.000 title abstract 8
- 150000001340 alkali metals Chemical class 0.000 title abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract 9
- -1 alkali metal salts Chemical class 0.000 abstract 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 abstract 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 abstract 6
- 239000003960 organic solvent Substances 0.000 abstract 4
- 239000000243 solution Substances 0.000 abstract 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 abstract 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 abstract 3
- 229940093499 ethyl acetate Drugs 0.000 abstract 3
- 235000019439 ethyl acetate Nutrition 0.000 abstract 3
- 239000000284 extract Substances 0.000 abstract 3
- 229940043265 methyl isobutyl ketone Drugs 0.000 abstract 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 3
- ITAMCOCNZJPJDF-UHFFFAOYSA-N 1-(6-aminopurin-9-yl)propan-2-yloxymethyl-phenoxyphosphinic acid Chemical compound C1=NC2=C(N)N=CN=C2N1CC(C)OCP(O)(=O)OC1=CC=CC=C1 ITAMCOCNZJPJDF-UHFFFAOYSA-N 0.000 abstract 2
- DLTWEQZAWUHBDH-UHFFFAOYSA-N 2-phenylpropanedioyl dichloride Chemical compound ClC(=O)C(C(Cl)=O)C1=CC=CC=C1 DLTWEQZAWUHBDH-UHFFFAOYSA-N 0.000 abstract 2
- IDJNJFYWPMDFNB-UHFFFAOYSA-N 3-oxo-3-phenoxy-2-phenylpropanoic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)C(=O)OC1=CC=CC=C1 IDJNJFYWPMDFNB-UHFFFAOYSA-N 0.000 abstract 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 abstract 2
- WWYDYZMNFQIYPT-UHFFFAOYSA-N ru78191 Chemical class OC(=O)C(C(O)=O)C1=CC=CC=C1 WWYDYZMNFQIYPT-UHFFFAOYSA-N 0.000 abstract 2
- 239000002904 solvent Substances 0.000 abstract 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract 2
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 abstract 1
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 abstract 1
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 abstract 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 abstract 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 abstract 1
- 150000008522 N-ethylpiperidines Chemical class 0.000 abstract 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 abstract 1
- 229930182555 Penicillin Natural products 0.000 abstract 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 150000001339 alkali metal compounds Chemical class 0.000 abstract 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 abstract 1
- 239000012670 alkaline solution Substances 0.000 abstract 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 abstract 1
- 239000011260 aqueous acid Substances 0.000 abstract 1
- 239000006286 aqueous extract Substances 0.000 abstract 1
- SHZIWNPUGXLXDT-UHFFFAOYSA-N caproic acid ethyl ester Natural products CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 abstract 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 abstract 1
- 150000007524 organic acids Chemical class 0.000 abstract 1
- 150000002960 penicillins Chemical class 0.000 abstract 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 abstract 1
- 229910052700 potassium Inorganic materials 0.000 abstract 1
- 239000011591 potassium Substances 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Cosmetics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
1,261,648. Crystalline alkali metal salts of α- carboxybenzyl-penicillin; penicillins and phenyl malonic acid derivatives. PFIZER Inc. 10 April, 1969 [17 Oct., 1968; 4 March, 1969], No. 18574/69. Headings C2A and C2C. Crystalline alkali metal salts of α-carboxybenzyl-penicillin are prepared by admixing a solution of α-carboxybenzylpenicillin (in a solvent selected from ethyl acetate, n-butanol, methylethyl ketone or methyl isobutylketone; the solution containing from 3 to 20% by weight of water) with an alkali metal compound selected from (a) an alkali metal salt of an organic acid selected from 2-ethyl hexanoic, caproic, oleic, ascorbic, glycolic, propionic, acetic, succinic, cinnamic, caprylic and nitric acids; (b) an alkali metal hydroxide; and (c) an alkali metal methoxide, wherein the alkali metal is sodium or potassium, and the product is isolated. The mono- or di-alkali metal salt may be prepared by employing a molar ratio of about 1 : 1 or at least 2 : 1 respectively of an alkali metal salt of group (a) to α-carboxybenzylpenicillin. The alkali metal salt of 2-ethyl hexanoic acid may be used in a solvent selected from acetone, ethyl acetate, n-butanol and isopropanol. A crystalline alkali metal salt of α-carboxy-benzylpenicillin may be prepared by (a) adjusting the pH of an aqueous alkaline solution of α-carboxybenzylpenicillin to 2 to 3À5; (b) extracting the acid solution thus produced with a waterimmiscible organic solvent selected from ethylacetate, n-butanol, methylethyl ketone and methyl isobutyl ketone; (c) back-extracting the water-immiscible organic solvent extract with water at pH 6À5 to 8À0; (d) adjusting the pH of the aqueous extract thus produced to a value of from 2 to 3À5; (e) extracting the aqueous acid solution thus produced with a water-immiscible organic solvent selected from n-butanol and methyl isobutyl ketone; (f) drying the water-immiscible organic solvent extract to a water content of from 3 to 20% by weight; (g) admixing the dried extract with an alkali metal 2-ethyl hexanoate; and (h) separating the crystalline alkali metal salt. α-Carboxybenzylpenicillin phenyl ester is prepared by reacting 6-aminopenicillanic acid with phenylmalonyl chloride monophenyl ester; and its N-ethyl piperidine salt is prepared by reaction with N-ethyl piperidine. Phenylmalonic acid monophenyl ester is prepared by reacting phenylmalonic acid with phosphorous oxychloride and phenol. Phenylmalonyl chloride monophenyl ester is prepared by reacting phenylmalonic acid monophenyl ester with thionyl chloride.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76849768A | 1968-10-17 | 1968-10-17 | |
| US80427569A | 1969-03-04 | 1969-03-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1261648A true GB1261648A (en) | 1972-01-26 |
Family
ID=27118061
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08574/69A Expired GB1261648A (en) | 1968-10-17 | 1969-04-10 | PROCESS FOR MAKING CRYSTALLINE ALKALI METAL SALTS OF alpha-CARBOXYBENZYL-PENICILLIN |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS5013328B1 (en) |
| AT (1) | AT303958B (en) |
| BE (1) | BE739920A (en) |
| CH (1) | CH515929A (en) |
| DE (1) | DE1950438C3 (en) |
| DK (1) | DK134347B (en) |
| ES (1) | ES372265A1 (en) |
| FI (1) | FI51814C (en) |
| FR (1) | FR2020883A1 (en) |
| GB (1) | GB1261648A (en) |
| IE (1) | IE33334B1 (en) |
| IL (1) | IL33061A (en) |
| NL (1) | NL6914872A (en) |
| NO (1) | NO138144C (en) |
| SE (1) | SE372770B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE758350A (en) * | 1969-12-30 | 1971-05-03 | Pfizer | MANUFACTURING PROCESS FOR MONO- AND BI-METALLIC ALKALINE SALTS OF ALPHA-CARBOXYBENZYLPENICILLIN |
| DE19901675A1 (en) * | 1999-01-18 | 2000-07-20 | Abb Patent Gmbh | Covering hood for thermal overcurrent relay, covers relay region near front, is held on relay housing by latching protrusions and latching points engaging side wall opposite attachment surface |
-
1969
- 1969-04-10 GB GB08574/69A patent/GB1261648A/en not_active Expired
- 1969-09-25 IL IL33061A patent/IL33061A/en unknown
- 1969-10-01 NL NL6914872A patent/NL6914872A/xx unknown
- 1969-10-06 CH CH1499269A patent/CH515929A/en not_active IP Right Cessation
- 1969-10-06 SE SE6913724A patent/SE372770B/xx unknown
- 1969-10-06 NO NO3982/69A patent/NO138144C/en unknown
- 1969-10-07 FI FI692891A patent/FI51814C/en active
- 1969-10-07 ES ES372265A patent/ES372265A1/en not_active Expired
- 1969-10-07 BE BE739920D patent/BE739920A/xx not_active IP Right Cessation
- 1969-10-07 IE IE1383/69A patent/IE33334B1/en unknown
- 1969-10-07 DE DE1950438A patent/DE1950438C3/en not_active Expired
- 1969-10-08 DK DK535269AA patent/DK134347B/en not_active IP Right Cessation
- 1969-10-08 FR FR6934356A patent/FR2020883A1/fr active Pending
- 1969-10-08 JP JP44080238A patent/JPS5013328B1/ja active Pending
- 1969-10-08 AT AT947069A patent/AT303958B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE1950438C3 (en) | 1975-06-19 |
| NO138144C (en) | 1978-07-12 |
| IL33061A0 (en) | 1969-11-30 |
| FI51814B (en) | 1976-12-31 |
| FI51814C (en) | 1977-04-12 |
| DE1950438B2 (en) | 1974-10-31 |
| NO138144B (en) | 1978-04-03 |
| DE1950438A1 (en) | 1970-04-23 |
| IE33334B1 (en) | 1974-05-29 |
| IL33061A (en) | 1973-04-30 |
| FR2020883A1 (en) | 1970-07-17 |
| ES372265A1 (en) | 1972-02-16 |
| SE372770B (en) | 1975-01-13 |
| CH515929A (en) | 1971-11-30 |
| AT303958B (en) | 1972-12-27 |
| BE739920A (en) | 1970-04-07 |
| DK134347B (en) | 1976-10-25 |
| IE33334L (en) | 1970-04-17 |
| JPS5013328B1 (en) | 1975-05-19 |
| DK134347C (en) | 1977-03-21 |
| NL6914872A (en) | 1970-04-21 |
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