Diisopropylamine → 2-(4-Methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (810 μL, 5.78 mmol) in dry tetrahydrofuran (4.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.5 mL) cooled to −78° C. was treated with a 2.5M solution of n-butyllithium in hexanes (2.3 mL, 5.78 mmol). The reaction mixture was stirred at −78° C. for 30 min and then treated with a solution of (4-methanesulfonyl-phenyl)-acetic acid methyl ester (prepared as in Example 8, 1.10 g, 4.82 mmol) in dry tetrahydrofuran (4.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.5 mL). The resulting reaction mixture was allowed to stir at −78° C. for 1 h and then the reaction mixture was treated with a solution of 2-(3-iodomethyl-cyclopentyloxy)-tetrahydropyran (prepared as in Example 35, 1.94 g, 6.26 mmol) in a small amount of dry tetrahydrofuran. The reaction mixture was stirred at −78° C. for 10 min and then allowed to warm to 25° C., where it was stirred for 3 d. The reaction mixture was quenched with water (50 mL) and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was further diluted with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 7/3 hexanes/ethyl acetate) afforded the 2-(4-methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester (1.07 g, 54%) as a yellow oil: FAB-HRMS m/e calcd for C21H30O6S (M+H)+ 411.1841, found 411.1851.

Provenance & Evidence