反应详情

温度

-78 °C

A stirred solution of trans-tert-butyl 4-(3-fluoro-4-methoxyphenyl)-3-hydroxypiperidine-1-carboxylate (100 mg, 0.31 mmol) in DCM (15 mL) at −78° C. was treated dropwise with DAST (0.08 mL, 0.6 mmol). The resulting mixture was stirred at −78° C. for 90 min. It was then quenched with ice water, warmed to rt, and extracted with DCM (50 mL). The organic layer was separated, washed with brine, dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to obtain 70 mg of (±)-rel-(3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate. LCMS (Method P) RT 1.11, 1.13 min, m/z 313 (M+H++CH3CN−t-butyl). Three batches of product (˜210 mg total) were combined and subjected to HPLC purification (Method A) to give 140 mg (±)-rel-(3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (s, 9H) 1.55-1.67 (m, 1H) 1.74-1.82 (m, 1H) 2.72-2.90 (m, 3H) 3.82 (s, 3H) 3.89-4.03 (m, 1H) 4.24-4.34 (m, 1H) 4.50-4.71 (m, 1H) 7.09 (d, J=1.51 Hz, 2H) 7.18-7.28 (m, 1H).

1. customIt was then quenched with ice water
2. temperaturewarmed to rt
3. extractionextracted with DCM (50 mL)
4. customThe organic layer was separated
5. washwashed with brine
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. customevaporated under reduced pressure