CN110256245A - A kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4- - Google Patents
A kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4- Download PDFInfo
- Publication number
- CN110256245A CN110256245A CN201910490571.0A CN201910490571A CN110256245A CN 110256245 A CN110256245 A CN 110256245A CN 201910490571 A CN201910490571 A CN 201910490571A CN 110256245 A CN110256245 A CN 110256245A
- Authority
- CN
- China
- Prior art keywords
- chloro
- bromobenzoic acid
- butyl ester
- acid tert
- synthetic method
- 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.)
- Pending
Links
- 238000010189 synthetic method Methods 0.000 title claims abstract description 10
- TVGYUWXKTIHRKA-UHFFFAOYSA-N tert-butyl 2-bromo-3-chlorobenzoate Chemical compound CC(C)(C)OC(=O)c1cccc(Cl)c1Br TVGYUWXKTIHRKA-UHFFFAOYSA-N 0.000 title claims abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 229940125904 compound 1 Drugs 0.000 claims description 3
- 229940125782 compound 2 Drugs 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims 1
- -1 tert-butyl tribromo-acetyl Imines ester Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 4
- USMQLFCVCDEXAK-UHFFFAOYSA-N 2-bromo-4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1Br USMQLFCVCDEXAK-UHFFFAOYSA-N 0.000 abstract description 2
- DVBLOOUJHBSMDI-UHFFFAOYSA-N CC(C)(C)OC(=O)c1ccc(Cl)cc1Br Chemical compound CC(C)(C)OC(=O)c1ccc(Cl)cc1Br DVBLOOUJHBSMDI-UHFFFAOYSA-N 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- CQXDYHPBXDZWBA-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroethanimidate Chemical compound CC(C)(C)OC(=N)C(Cl)(Cl)Cl CQXDYHPBXDZWBA-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 1
- SITHNMNGOHVILG-UHFFFAOYSA-N 2-bromo-3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1Br SITHNMNGOHVILG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/24—Preparation of carboxylic acid esters by reacting carboxylic acids or derivatives thereof with a carbon-to-oxygen ether bond, e.g. acetal, tetrahydrofuran
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/56—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of synthetic methods of the chloro- 2- bromobenzoic acid tert-butyl ester of 4-, the technical issues of mainly solution currently without suitable Industrialized synthesis method.The present invention is a step, is that compound 4-chloro -2- bromobenzoic acid and tert-butyl tri- chloroacetimidate act in methylene chloride and obtain the compound 4-chloro -2- bromobenzoic acid tert-butyl ester.Reaction equation is as follows:
Description
Technical field
The present invention relates to the synthetic methods of the compound 4-chloro -2- bromobenzoic acid tert-butyl ester.
Background technique
Compound 4-chloro -2- bromobenzoic acid the tert-butyl ester (MFCD29962773) and relevant derivative in pharmaceutical chemistry and have
Have in machine synthesis and is widely applied.The chloro- 2- bromobenzoic acid tert-butyl ester synthetic method of 4- rarely has document report at present.Therefore, it is necessary to
A raw material is developed to be easy to get, it is easy to operate, react easily controllable, overall yield is suitble to, and is suitble to the synthetic method of industrialized production.
Summary of the invention
It is easy to operate the purpose of the present invention is developing one kind to be easy to get with raw material, react easily controllable, the higher 4- of yield
The synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester.The technical issues of mainly solving currently without suitable Industrialized synthesis method.
Technical solution of the present invention: a kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4-, the present invention totally one step are
Compound 1 and tert-butyl tri- chloroacetimidate act in methylene chloride obtains compound 2.Reaction equation is as follows:
This step reaction is 20 DEG C of 12 hours of reaction.
The Chinese paraphrase that the present invention abridges: DCM: methylene chloride.
Beneficial effects of the present invention: reaction process of the present invention design rationally, which employs be easy to get, can large-scale production original
Expect the chloro- 2- bromobenzoic acid of 4-, by the chloro- 2- bromobenzoic acid tert-butyl ester of one-step synthesis 4-, this method route is short, and yield may be up to
85%, reaction is easy to amplify, easy to operate.
Specific embodiment
Reaction equation of the present invention is as follows:
Embodiment 1:
Compound 1(81.00 g, 344.01 mmol) is dissolved in methylene chloride (1.1 L), then tert-butyl is added dropwise in room temperature
Tri- chloroacetimidate (300.68 g, 1.38 mol) reacts 12 hours, TLC (petrol ether/ethyl acetate body at 20 DEG C
Product ratio=5/1) display end of reaction.Reaction system addition 1.5L water is quenched, then uses methylene chloride (3*0.5L)
It is extracted, organic phase brine It, then drying is concentrated to get crude product, carries out column chromatography for separation purification (petroleum later
Ether/ethyl acetate volume ratio=50/ to 5/1) obtain compound 2(85 g).Yield 85%.
HNMR:CDCl3 δ = 7.60 - 7.52 (m, 2H), 7.23 (dd, J=2.0, 8.4 Hz, 1H),
1.52 (s, 9H) 。
Claims (2)
1. a kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4-, it is characterized in that: by compound 1 and tert-butyl tribromo-acetyl
Imines ester acts in methylene chloride and obtains compound 2；Reaction equation is as follows:
。
2. the synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of a kind of 4- according to claim 1, it is characterized in that: reaction temperature
20 DEG C, the reaction time 12 hours of degree.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910490571.0A CN110256245A (en) | 2019-06-06 | 2019-06-06 | A kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4- |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910490571.0A CN110256245A (en) | 2019-06-06 | 2019-06-06 | A kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4- |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110256245A true CN110256245A (en) | 2019-09-20 |
Family
ID=67917125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910490571.0A Pending CN110256245A (en) | 2019-06-06 | 2019-06-06 | A kind of synthetic method of the chloro- 2- bromobenzoic acid tert-butyl ester of 4- |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110256245A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105008347A (en) * | 2013-03-11 | 2015-10-28 | 百时美施贵宝公司 | Isoquinolines as potassium ion channel inhibitors |
| WO2019081559A1 (en) * | 2017-10-25 | 2019-05-02 | Les Laboratoires Servier | Novel macrocyclic derivatives, process for preparing same and pharmaceutical compositions containing same |
-
2019
- 2019-06-06 CN CN201910490571.0A patent/CN110256245A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105008347A (en) * | 2013-03-11 | 2015-10-28 | 百时美施贵宝公司 | Isoquinolines as potassium ion channel inhibitors |
| WO2019081559A1 (en) * | 2017-10-25 | 2019-05-02 | Les Laboratoires Servier | Novel macrocyclic derivatives, process for preparing same and pharmaceutical compositions containing same |
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| PB01 | Publication | ||
| PB01 | Publication | ||
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190920 |