Lithium Hydroxide → HCID 21051840, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(4-fluoro-3-trifluoromethyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (1.97 g, 6.15 mmol) in dry N,N-dimethylformamide (20 mL) at 25° C. under argon was carefully treated with sodium thiomethoxide (0.680 g, 9.27 mmol) and was then heated at 100° C. for 3 h. The reaction mixture was then concentrated in vacuo to remove N,N-dimethylformamide. The remaining residue was suspended in a saturated aqueous ammonium chloride solution (100 mL) and was extracted with ethyl acetate (2×200 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was then dissolved in methanol (40 mL) and was treated with a 0.8M aqueous lithium hydroxide solution (20.60 mL, 16.7 mmol). The reaction mixture was stirred at 25° C. for 16 h and then was concentrated in vacuo to remove methanol. The remaining aqueous layer was acidified to pH=2 with a 10% aqueous hydrochloric acid solution and then was extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford pure 2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-3(tetrahydro-furan-2(R)-yl)-propionic acid (1.71 g, 83%) as a light yellow oil: [α]23589=−23.26° (c=0.49, chloroform); EI-HRMS m/e calcd for C15H17F3O3S (M−H2O)+ 316.0744, found 316.0749.

Provenance & Evidence