Diisopropylamine → HCID 21958996, compound

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (7.04 mL, 49.97 mmol) in dry tetrahydrofuran (140 mL) cooled to −78° C. under argon was treated with a 2.5M solution of n-butyllithium in hexanes (19.8 mL, 49.5 mmol). The reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (4-fluoro-3-trifluoromethyl-phenyl)-acetic acid (5.00 g, 22.51 mmol) in dry tetrahydrofuran (25 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (8.5 mL). The reaction mixture turned gold in color and was allowed to stir at −78° C. for 1 h. At this time, the reaction was treated with a solution of trifluoromethanesulfonic acid tetrahydro-pyran-2-yl methyl ester (7.26 g, 29.26 mmol) in dry tetrahydrofuran (100 mL). The reaction mixture was allowed to warm to 25° C., where it was stirred for 30 min. The reaction mixture then was quenched with a saturated aqueous ammonium chloride solution (100 mL) and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was acidified to pH=2 using a 1N aqueous hydrochloric acid solution. The resulting aqueous layer was extracted with ethyl acetate (2×250 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/7 hexanes/ethyl acetate to 1/1 hexanes/ethyl acetate) afforded 2-(4-fluoro-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid (5.20 g, 72%) as a yellow gum: EI-HRMS m/e calcd for C15H16F4O3 (M+Na)+ 343.0931. found 343.0928.

Provenance & Evidence