(Diethylamino)sulfur trifluoride → (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate

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Reaction Steps

To (3S,4S)-tert-butyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylate (2.99 g, 9.60 mmol) in DCM (75 mL) at 0° C. was added DAST (6.34 mL, 48.0 mmol) dropwise. The reaction was then allowed to warm to room temperature and stir for 2 h. The reaction was slowly quenched with ice water. The reaction was then extracted with dichloromethane, washed with additional water, dried with magnesium sulfate, filtered and concentrated in vacuo to afford (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate (3.88 g, quantitative yield) as a yellow viscous oil: LC-MS [M−H]+ 312.2; 1H NMR (500 MHz, DMSO-d6) δ 7.22-7.10 (m, 1H), 7.00-6.76 (m, 3H), 5.76 (s, 2H), 4.60 (td, J=10.1, 5.2 Hz, 1H), 4.50 (td, J=10.1, 5.2 Hz, 1H), 4.27 (br. s., 1H), 4.07-3.78 (m, 2H), 3.66-3.50 (m, 1H), 3.00-2.65 (m, 4H), 1.81-1.69 (m, 1H), 1.63-1.50 (m, 1H), 1.46-1.30 (m, 14H), 1.20-1.01 (m, 2H).

Provenance & Evidence