Preparation process of lubiprostone intermediate

Abstract

The invention discloses a preparation process of a lubiprostone intermediate. The preparation process comprises the following steps: firstly, carrying out reduction reaction on a lubi-initiator to obtain an intermediate 1; secondly, adding excessive weak base into a mixed solution of triphenylphosphonic acid bromide and absolute ether, then adding the intermediate 1 for complete reaction, then adjusting a pH value to 5 to 6, adding ethyl acetate for extracting, combining organic layers to obtain an organic phase, and carrying out vacuum concentration and drying on the organic phase to obtain an intermediate 2; thirdly, adding acetonitrile, diisopropylethylamine and benzyl bromide into the intermediate 2 for complete reaction, then carrying out vacuum concentration and drying, and adding the ethyl acetate and water for extracting and separating liquid; carrying out vacuum concentration and drying on the organic phase to obtain a crude product of an intermediate 3. The preparation process disclosed by the invention has the advantages of rapid and convenient synthesis route, high yield and relatively high economic value; the preparation process is quite suitable for scale production and provides another synthesis route with high economic benefits and high production efficiency for producing lubiprostone.

Description

technical field

[0001] The invention relates to the field of sewage treatment and environmental protection, in particular to a preparation process of a lubiprostone intermediate. Background technique

[0002] Lubiprostone is a chemical constipation treatment drug. It is the only prescription drug approved in Switzerland for the treatment of long-term chronic idiopathic constipation. Compared with other laxatives, it not only has a good constipation treatment effect, but also has long-term drug resistance The incidence of sex is low, and it also has the advantages of small doses.

[0003] The structure of lubiprostone is primarily a 20-carbon acid with a five-membered aliphatic ring with two side chains. Among them, the five-membered ring contains multiple chiral carbon atoms and two side chains. These chiral carbon atoms respectively control the configuration of each chiral center, making the stereoselective synthesis difficult.

[0004] (Z)-7-[(1R,2R,3R,5S)-2-(4,4-difluor...