4-(Trifluoromethyl)benzenemethanol → HCID 68884763, compound

Participants

Reaction Steps

4-(Trifluoromethyl)benzyl alcohol (0.88 g, 5.0 mmol) was dissolved in toluene (5 mL) and followed by the addition of 1,1′-carbonyldiimidazole (0.89 g, 5.5 mmol). The resulting mixture was stirred under nitrogen at rt for 1 h. A solution of (3S)-2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid methyl ester (Preparation 2; Method E) (1.39 g, 5.0 mmol) in toluene (8 mL) was then introduced and the reaction mixture was heated at 60° C. for 2 h. After cooling, the reaction solution was diluted with ethyl acetate (30 mL) and washed with 1 M HCl (30 mL) and brine (30 mL). The separated organic layer was dried over sodium sulfate and concentrated to yield 2.43 g (100%) of (3S)-3-[3-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester as a light yellow oil: 1H NMR (CDCl3) δ 1.58 (s, 8H), 1.77 (br m, 1H), 2.00 (br m, 1H), 2.61 (br, 1H), 2.80 (br, 2H), 3.74 (s, 3H), 4.21 (br s, 2H), 5.19 (s, 2H), 6.63 (dd, 1H), 6.72 (s, 1H), 6.83 (br d, 1H), 7.16 (t, 1H), 7.46 (br s, 2H), 7.60 (d, 2H); MS m/z (relative intensity) 479 (M+, 25), 420 (20), 395 (20), 276 (20), 220 (60), 202 (42), 176 (45), 159 (100).

Provenance & Evidence