Sodium bis(trimethylsilyl)amide → 2-(3-Chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-acrylic acid ethyl ester

Temperature

0 °C

A solution of cylcopentylmethyl triphenylphosphonium iodide (prepared in Example 33, 725 mg, 1.53 mmol) in tetrahydrofuran (10 mL) cooled to 0° C. was treated with a 1.0M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (2.14 mL, 2.14 mmol). The reaction was stirred at 0° C. for 45 min. At this time, the reaction was treated with a solution of (3-chloro-4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (355 mg, 1.37 mmol) in tetrahydrofuran (5 mL). The reaction was then warmed to 25° C. and stirred at 25° C. for 20 h. The reaction was then diluted with water (50 mL) and extracted with diethyl ether (3×25 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 80/20 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-acrylic acid ethyl ester (267 mg, 60%, 2:1 mixture of E:Z isomers) as a yellow oil and taken on without characterization.

1. temperatureThe reaction was then warmed to 25° C.
2. stirringstirred at 25° C. for 20 h
3. extractionextracted with diethyl ether (3×25 mL)
4. dry with materialThe organics were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-7f138fe89d57439d8338936c6798aea1

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1