Diisopropylamine → 3-Cyclopentyl-2-(3-trifluoromethylsulfanyl-phenyl)-propionic acid methyl ester

Temperature

-78 °C

A solution of diisopropylamine (1.5 mL, 10.5 mmol) in dry tetrahydrofuran (27 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (8 mL) cooled to −78° C. was treated with a 2.5M solution of n-butyllithium in hexanes (4.2 mL, 10.5 mmol). The resulting reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3-trifluoromethylsulfanyl-phenyl)-acetic acid methyl ester (2.50 g, 10.0 mmol) in a small amount of tetrahydrofuran. The reaction mixture was allowed to stir at −78° C. for 1 h. At this time, the reaction was treated with a solution of iodomethylcyclopentane (2.10 g, 10.0 mmol) in a small amount of dry tetrahydrofuran. The reaction mixture was allowed to warm to 25° C. where it was stirred for 15 h. The reaction mixture was quenched with water (50 mL) and then partitioned between water (75 mL) and ethyl acetate (75 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 8/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3-trifluoromethylsulfanyl-phenyl)-propionic acid methyl ester (2.95 g, 89%) as a colorless oil: EI-HRMS m/e calcd for C16H19F3O2S (M+) 332.1058, found 332.1047.

1. customThe resulting reaction mixture
2. stirringto stir at −78° C. for 1 h
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 15 h
5. customThe reaction mixture was quenched with water (50 mL)
6. custompartitioned between water (75 mL) and ethyl acetate (75 mL)
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-46040b9cd753400f9b720760dd01e048

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1