Synthesis method of tert-butyl bromoacetate

Abstract

The invention relates to a synthesis method of tert-butyl bromoacetate, and the synthesis method comprises the following steps of: mixing bromoacetic acid and tert-butyl acetate at a weight ratio of 4:(1-1):1, and completely dissolving bromoacetic acid in tert-butyl acetate; then, feeding the solution into a reactor filled with strong acid type ion exchange resin, controlling the temperature within the range of 30-45 DEG C, reacting for 2-6 hours, and generating a mixture with 30-35% tert-butyl bromoacetate; and separating by two rectifying towers, thus obtaining the tert-butyl bromoacetate with the purity of more than 99%, wherein more than 90% of tert-butyl acetate is completely reacted, and the effective transformation rate of the tert-butyl bromoacetate is more than 80%. According to the invention, the original technology is changed, a two-step production method is replaced by a one-step production method, and the tert-butyl acetate is used for replacing the original thionyl chloride with strong corrosivity and irritation and taken as a raw material, so that the three wastes are not produced in the production process, and the synthesis method is in accordance with the environmental protection policy of China.

Description

technical field

[0001] The invention belongs to the field of organic compound synthesis, in particular to a synthesis method of tert-butyl bromoacetate. Background technique

[0002] Tert-butyl bromoacetate is an important pharmaceutical intermediate. The production method mainly used at home and abroad is described in the document "Simple Synthesis Method of Tert-Butyl Bromoacetate". This method is a two-step method, and the main process is described as follows :

[0003] Bromoacetic acid + thionyl chloride → bromoacetyl chloride

[0004] Bromoacetyl chloride + tert-butanol → tert-butyl bromoacetate + hydrogen chloride

[0005] In the reaction laboratory data, thionyl chloride is excessive, and the yield of bromoacetyl chloride is 95%. The technological process will adopt atmospheric distillation and vacuum distillation successively, and the bromoacetyl chloride obtained by the reaction, then bromoacetyl chloride and tert- Butanol reaction, using sodium tripolyphosphate...

Examples

Embodiment 1

[0021] Take 120 grams of bromoacetic acid and 40 grams of tert-butyl acetate, put the bromoacetic acid into the solution of tert-butyl acetate, put it in a closed container, and then put it in a constant temperature box at a constant temperature of 40°C. After 2 hours, , the bromoacetic acid solid is completely dissolved, and then enters the chromatograph for analysis. The main peaks are two substances, and then the mixed solution is put into a container with 60 grams of strong acid ion exchange resin catalyst (the catalyst must be dry In the first 10 hours, the catalyst has an expansion process, and the reaction is slower. When the catalyst expands in place, the reaction speeds up, and the newly foamed catalyst The reaction time is longer, and after 14 hours, a sample is taken for analysis, and the reactant of the following composition is obtained: acetic acid, 11.9%; tert-butyl acetate, 2.6%; C 8 (diisobutylene), 2.2%; bromoacetic acid, 48.5%; tert-butyl bromoacetate, 34.5%...

Embodiment 2

[0023] Filter out the material in the catalyst that has been catalyzed, reconstitute 120 grams of bromoacetic acid, 40 grams of tert-butyl acetate, put bromoacetic acid in the solution of tert-butyl acetate, put it in a closed container, and then put Put it into a constant temperature box at a constant temperature of 40°C. After 2 hours, the bromoacetic acid solid is completely dissolved, and then enter the chromatograph for analysis. The main peaks are two substances, and then put the mixed solution into the catalyst used for the reaction. The reaction was carried out in a constant temperature chamber, and the constant temperature was 40°C. After 4 hours, the sample was analyzed to obtain a reactant with the following composition: acetic acid, 11.5%; tert-butyl acetate, 2.9.%; C 8 (diisobutylene), 1.8%; bromoacetic acid, 50.1%; tert-butyl bromoacetate, 33.5%; C 12 , 0.2%.

technical field

[0001] The invention belongs to the field of organic compound synthesis, in particular to a synthesis method of tert-butyl bromoacetate. Background technique

[0002] Tert-butyl bromoacetate is an important pharmaceutical intermediate. The production method mainly used at home and abroad is described in the document "Simple Synthesis Method of Tert-Butyl Bromoacetate". This method is a two-step method, and the main process is described as follows :

[0003] Bromoacetic acid + thionyl chloride → bromoacetyl chloride

[0004] Bromoacetyl chloride + tert-butanol → tert-butyl bromoacetate + hydrogen chloride

[0005] In the reaction laboratory data, thionyl chloride is excessive, and the yield of bromoacetyl chloride is 95%. The technological process will adopt atmospheric distillation and vacuum distillation successively, and the bromoacetyl chloride obtained by the reaction, then bromoacetyl chloride and tert- Butanol reaction, using sodium tripolyphosphate...

Examples

Embodiment 1

[0021] Take 120 grams of bromoacetic acid and 40 grams of tert-butyl acetate, put the bromoacetic acid into the solution of tert-butyl acetate, put it in a closed container, and then put it in a constant temperature box at a constant temperature of 40°C. After 2 hours, , the bromoacetic acid solid is completely dissolved, and then enters the chromatograph for analysis. The main peaks are two substances, and then the mixed solution is put into a container with 60 grams of strong acid ion exchange resin catalyst (the catalyst must be dry In the first 10 hours, the catalyst has an expansion process, and the reaction is slower. When the catalyst expands in place, the reaction speeds up, and the newly foamed catalyst The reaction time is longer, and after 14 hours, a sample is taken for analysis, and the reactant of the following composition is obtained: acetic acid, 11.9%; tert-butyl acetate, 2.6%; C 8 (diisobutylene), 2.2%; bromoacetic acid, 48.5%; tert-butyl bromoacetate, 34.5%...

Embodiment 2

[0023] Filter out the material in the catalyst that has been catalyzed, reconstitute 120 grams of bromoacetic acid, 40 grams of tert-butyl acetate, put bromoacetic acid in the solution of tert-butyl acetate, put it in a closed container, and then put Put it into a constant temperature box at a constant temperature of 40°C. After 2 hours, the bromoacetic acid solid is completely dissolved, and then enter the chromatograph for analysis. The main peaks are two substances, and then put the mixed solution into the catalyst used for the reaction. The reaction was carried out in a constant temperature chamber, and the constant temperature was 40°C. After 4 hours, the sample was analyzed to obtain a reactant with the following composition: acetic acid, 11.5%; tert-butyl acetate, 2.9.%; C 8 (diisobutylene), 1.8%; bromoacetic acid, 50.1%; tert-butyl bromoacetate, 33.5%; C 12 , 0.2%.