Hydrochloric Acid → 3-Cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-propionic acid methyl ester

Temperature

105 °C

A solution of 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid methyl ester (7.0 g, 21.9 mmol) in N,N-dimethylformamide (50 mL) was treated with sodium methanethiolate (2.61 g, 33.0 mmol). The reaction mixture was then heated at 100-110° C. for 24 h. At this time, the reaction was poured onto a mixture of ice and a 2N aqueous hydrochloric acid solution (100 mL). This mixture was extracted into ethyl acetate (3×75 mL) and diethyl ether (1×50 mL). The combined organic layers were then washed with water (1×75 mL) and a saturated aqueous sodium chloride solution (3×100 mL). The organic layer was dried over magnesium sulfate and sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 85/15 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-propionic acid methyl ester (2.48 g, 35.5%) as a pale yellow oil: EI-HRMS m/e calcd for C17H21F3O2S (M+) 346.1214, found 346.1212.

1. additionAt this time, the reaction was poured onto a mixture of ice
2. extractionThis mixture was extracted into ethyl acetate (3×75 mL) and diethyl ether (1×50 mL)
3. washThe combined organic layers were then washed with water (1×75 mL)
4. dry with materialThe organic layer was dried over magnesium sulfate and sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-063d86c4b86e4b0386805c0716bac45c

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06433188B1