Thionyl Chloride → HCID 71008696, compound

Temperature

85 °C

A solution of (1S,2S)-rel-2-[(R)-2,2-difluoro-3-hydroxy-1-methyl-1-((R)-2-methyl-propane-2-sulfinylamino)-propyl]-cyclopropanecarboxylic acid tert-butyl ester (1.16 g, 3.14 mmol) in ethanol (22.5 ml) was treated dropwise at 0° C. with thionyl chloride (1.89 g, 1.15 ml, 15.7 mmol). The yellow mixture was then stirred at 85° C. for 2 hours. For the workup, the solvent was evaporated at reduced pressure, then water and diethyl ether were added. The aqueous layer was treated with carbonate, thereafter extracted three times with dichloromethane. The combined organic layers were dried over sodium sulphate and evaporated. The light yellow oil (708 mg) was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent. The (1S,2S)-rel-2-((R)-1-amino-2,2-difluoro-3-hydroxy-1-methyl-propyl)-cyclopropane-carboxylic acid ethyl ester (566 mg, 76% yield) was obtained as a light yellow oil. MS (ISP): m/z=238.2 [M+H]+.

1. customFor the workup, the solvent was evaporated at reduced pressure
2. additionwater and diethyl ether were added
3. additionThe aqueous layer was treated with carbonate
4. extractionextracted three times with dichloromethane
5. dry with materialThe combined organic layers were dried over sodium sulphate
6. customevaporated
7. customThe light yellow oil (708 mg) was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent

ORD record

ord-d80c02a53e9f4c82942ca71e79cf6684

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785436B2