Hydrochloric Acid → 3-Cyclopentyl-2-(4-methylsulfanyl-phenyl)-acrylic acid ethyl ester

Temperature

0 °C

A suspension of cyclopentylmethyl triphenylphosphonium iodide (151.73 g, 0.321 mol) in dry tetrahydrofuran (494 mL) was cooled to 0° C. and then treated slowly with a 1.0 M solution of lithium bis(trimethylsilyl)amide (309 mL, 0.309 mol). The bright orange reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was then treated with a solution of (4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (55.42 g, 0.247 mol) in dry tetrahydrofuran (100 mL) in small portions. The resulting reaction mixture was stirred at 0° C. for 30 min and then allowed to warm to 25° C. where it was stirred for 6 h. The reaction mixture was then diluted with water (500 mL), at which time, the reaction mixture indicated a pH=11. The reaction mixture was adjusted to pH=6 with a 10% aqueous hydrochloric acid solution and then allowed to sit at 25° C. overnight. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran and then diluted with diethyl ether (1 L). A solid began to precipitate, and the reaction mixture was allowed to sit at 25° C. for 1 h. The solid was filtered and washed well with diethyl ether. The resulting two-layer filtrate was transferred to a separatory funnel, and the layers were separated. The aqueous layer was further extracted with diethyl ether (1×500 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×500 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification using a plug of silica (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methylsulfanyl-phenyl)-acrylic acid ethyl ester (58.93 g, 82%) as a yellow oil consisting of a 1.44:1 mixture of (E):(Z) isomers. The material was used without further separation and characterization.

1. customThe resulting reaction mixture
2. stirringwas stirred at 0° C. for 30 min
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 6 h
5. waitto sit at 25° C. overnight
6. concentrationThe reaction mixture was concentrated in vacuo
7. customto remove tetrahydrofuran
8. additiondiluted with diethyl ether (1 L)
9. customto precipitate
10. waitto sit at 25° C. for 1 h
11. filtrationThe solid was filtered
12. washwashed well with diethyl ether
13. customThe resulting two-layer filtrate was transferred to a separatory funnel
14. customthe layers were separated
15. extractionThe aqueous layer was further extracted with diethyl ether (1×500 mL)
16. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (1×500 mL)
17. dry with materialdried over sodium sulfate
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. customPurification

ORD record

ord-6c4c39061b2c4a7ab5ac6d33d1999e7a

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353111B1