Sodium bis(trimethylsilyl)amide → 3-Cyclopentyl-2-(4-ethylsulfanyl-phenyl)-acrylic acid ethyl ester

Temperature

0 °C

A suspension of cyclopentylmethyl triphenylphosphonium iodide (24.48 g, 51.82 mmol) in tetrahydrofuran (100 mL) cooled to 0° C. was treated dropwise with a 1.0M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (52 mL, 51.82 mmol). The bright orange reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was then treated with (4-ethylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (9.50 g, 39.87 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 20 h. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran and then diluted with water (300 mL). The aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 19/1 hexanes/ethyl acetate) afforded the 3-cyclopentyl-2-(4-ethylsulfanyl-phenyl)-acrylic acid ethyl ester (6.08 g, 50%) as a yellow oil containing a 1.82:1 mixture of E:Z isomers: FAB-LRMS m/e calcd for C18H24O2S (M+H)+integer mass 304, found 305.

1. customThe resulting reaction mixture
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 20 h
4. concentrationThe reaction mixture was concentrated in vacuo
5. customto remove tetrahydrofuran
6. additiondiluted with water (300 mL)
7. extractionThe aqueous layer was extracted with ethyl acetate (3×200 mL)
8. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (1×200 mL)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-5c2d9b3fa4e64cbe90b3222f72e03bde

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1