Nitrogen → HCID 86639445, compound

Participants

Reaction Conditions

Reaction Steps

Under protection of N2, 1,2-difluorobenzene (22 g, 0.19 mol) in anhydrous THF (300 mL) was cooled to −78° C. and 2.5 M n-BuLi solution in hexanes (76 mL, 0.19 mol) was added dropwise slowly. The reaction mixture was stirred at −78° C. for 1 hr, the solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (47.7 g, 0.175 mol) in anhydrous THF (200 mL) was slowly added dropwise. The reaction mixture warmed to rt and stirred for 2 hrs. The mixture was quenched with saturated NH4Cl (300 mL), extracted three times with ethyl acetate, and dried over Na2SO4. Solvent removal and flash column chromatography afforded crude (R)-tert-butyl 3-(2,3-difluorobenzoyl)piperidine-1-carboxylate (R)-tert-butyl 3-(2,3-difluorobenzoyl)piperidine-1-carboxylate (40 g, 70%). 1H NMR (CDCl3, 400 MHz) δ 7.51 (m, 1H), 7.34 (m, 1H), 7.19 (m, 1H), 4.19 (d, 1H), 3.96 (m, 1H), 3.23 (m, 1H), 3.04 (t, 1H), 2.85 (m, 1H), 2.06 (m, 1H), 1.75 (m, 1H), 1.62 (m, 4H), 1.44 (s, 9H).

Provenance & Evidence