WO1998055445A1

WO1998055445A1 - A process for the preparation of 1-bromoethyl acetate

Info

Publication number: WO1998055445A1
Application number: PCT/KR1998/000135
Authority: WO
Inventors: You Wha Hong; Yaung Chul Shin; Ja Heouk Khoo
Original assignee: Yuhan Corporation
Priority date: 1997-06-03
Filing date: 1998-05-29
Publication date: 1998-12-10
Also published as: KR19990006498A; KR100401284B1

Abstract

The present invention relates to a process for preparing 1-bromoethyl acetate which comprises reacting vinyl acetate with hydrogen bromide. According to the present invention, 1-bromoethyl acetate can be prepared in a high yield, without using acetaldehyde, acetyl bromide, and a heavy metal containing compound such as zinc chloride.

Description

A PROCESS FOR THE PREPARATION OF 1-BROMOETHYL

ACETATE

Technical Field

The present invention relates to a novel process for the preparation of 1-bromoethyl acetate. More particularly, the present invention relates to a process for preparing 1 -bromoethy 1 acetate which comprises reacting vinyl acetate with hydrogen bromide.

Background Art

1 -Bromoethy 1 acetate is an intermediate useful for preparing cefuroxime axetil which is one of oral cephalosporin antibiotics. For example, European Patent No. 757,991 discloses a process for preparing 1 -bromoethy 1 acetate by reacting acetyl bromide with acetaldehyde using zinc chloride as a catalyst. The reaction scheme is shown as follows:

Scheme 1

o 0 ZnCI, Br ^ ^H n H₃ rC. -^ B ^Br^r μ H₃ rCv -L

H₃C - ^ ^ϋ CH₃

However, acetyl bromide is very unstable against water and the boiling point of acetaldehyde is very low, which gives rise to problems in applying to large scale synthesis. Further, acetaldehyde is a cancer suspected material and especially, zinc chloride used as a catalyst in the above process is zinc (one of heavy metals) containing compound which may cause an environmental pollution. Disclosure of Invention

Thus, the present inventors have carried out an extensive research to develop a novel process for the preparation of 1-bromoethyl acetate which can solve the disadvantages involved in the prior art. As a result, we have discovered that when reacting vinyl acetate with hydrogen bromide, 1-bromoethyl acetate can be prepared in a high yield, without using acetyl bromide, acetaldehyde, and a heavy metal containing compound such as zinc chloride. The present invention is based on such discovery.

Accordingly, it is an object of the present invention to provide a novel process for preparing 1-bromoethyl acetate which comprises reacting vinyl acetate with hydrogen bromide.

In accordance with the present invention, 1-bromoethyl acetate may be prepared by reacting vinyl acetate with hydrogen bromide in accordance with Scheme 2 described below.

Scheme 2

HBr

Jx J-L

H ',3C^U 3

The reactants in the Scheme 2, vinyl acetate and hydrogen bromide, are manufactuered in a large scale. Therefore, those are commercially available and inexpensive.

As shown in the Scheme 2, hydrogen bromide may be directly reacted with vinyl acetate, preferably in the presence of solvent, to obtain 1-bromoethyl acetate in a high yield. Suitable solvent for use in the process of the present invention may include organic acid solvent such as acetic acid, which can solubilize hydrogen bromide.

In the process of the present invention, the amount of hydrogen bromide to react with vinyl acetate preferably ranges from 1 eq. to 3 eq. to vinyl acetate to obtain 1-bromoethyl acetate in a high yield. The reaction temperature preferably ranges from 0"C to 10 "C , considering that the side reactions can be reduced in such temperature range. Further, the reaction time preferably ranges from 1 hour to 2 hours.

As shown in the following Examples, 1 -bromoethy 1 acetate may be obtained by carrying out the process of the present invention without using acetyl bromide, acetaldehyde, and a heavy metal containing compound as a catalyst.

The following Examples are given for the purpose of illustration only, and are not intended to limit the scope of the invention.

Example 1

After 150 ml(1.2 e.q.) of a solution of hydrogen bromide(30%) in acetic acid was cooled to 0 ^°C , 53.5 m#(1.0 e.q.) of vinyl acetate was slowly added to the mixture. The reaction mixture was stirred for 1 hour and then extracted with dichloromethane. The extract was washed with distilled water(0"C -5°C ), dehydrated over anhydrous magnesium sulfate, and then distilled under vacuum to obtain 81.4 g of 1-bromoethyl acetate.

Yield : 84.0 %

NMR(CDCb) : δ = 6.68 (1H, q, CHBr); 2.17 (3H, s, COCHs); 1.96 (3H, d,

CHsCHBr)

Example 2 After 118 mKl.O e.q.) of a solution of hydrogen bromide(30%) in acetic acid was cooled to 0 ^°C , 53.5 m#(1.0 e.q.) of vinyl acetate was slowly added to the mixture. The reaction mixture was stirred for 1 hour and then extracted with dichloromethane. The extract was washed with distilled water(0^°C -5^°C ), dehydrated over anhydrous magnesium sulfate, and then distilled under vacuum to obtain 81.08 g of 1-bromoethyl acetate. (Yield : 83.7 %)

Example 3

After 237 ml(2.0 e.q.) of a solution of hydrogen bromide(30%) in acetic acid was cooled to 0 ^°C, 53.5 l(1.0 e.q.) of vinyl acetate was slowly added to the mixture. The reaction mixture was stirred for 1 hour and then extracted with dichloromethane. The extract was washed with distilled water(0^°C -5^"C ), dehydrated over anhydrous magnesium sulfate, and then distilled under vacuum to obtain 80.8 g of 1 -bromoethy 1 acetate. (Yield : 83.5 %)

Example 4

After 356 ml(3.0 e.q.) of a solution of hydrogen bromide (30%) in acetic acid was cooled to 0 ^°C, 53.5 td.O e.q.) of vinyl acetate was slowly added to the mixture. The reaction mixture was stirred for 1 hour and then extracted with dichloromethane. The extract was washed with distilled water(0^°C -5^°C), dehydrated over anhydrous magnesium sulfate, and then distilled under vacuum to obtain 82.3 g of 1 -bromoethy 1 acetate. (Yield : 85.0 %)

Claims

WHAT IS CLAIMED IS :

1. A process for preparing 1-bromoethyl acetate which comprises reacting vinyl acetate with hydrogen bromide.

2. The process as claimed in claim 1, wherein the reaction is carried out in the presence of an organic acid solvent.

3. The process as claimed in claim 2, wherein the organic acid solvent is acetic acid.

4. The process as claimed in claim 1, wherein the amount of hydrogen bromide ranges from 1 eq. to 3 eq. with respect to vinyl acetate.

5. The process as claimed in claim 1, wherein the reaction temperature ranges from 0^┬░C to 10 ^┬░C .