Dimethyl Sulfoxide → HCID 118207506, compound

Participants

Reaction Steps

To a solution of DMSO (3.7 mL, 52 mmol) in 50 mL of DCM under nitrogen at −78° C. was added oxalyl chloride (4.45 mL, 51 mmol). The mixture was stirred for 10 minutes after the completion of the addition. Then a solution of (±)-rel-(3S,4S)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-hydroxypiperidine-1-carboxylate (from Example 50, step D, 6.5 g, 17 mmol) in 50 mL of DCM was added and the mixture was stirred in the cold for a further 90 minutes. The reaction was then quenched by the addition of 11.8 mL of triethylamine (85 mmol) and allowed to warm up to rt. The mixture was then partitioned between 200 mL brine and 200 mL DCM. The layers were separated, and the organic layer was dried over Na2SO4, filtered, and concentrated. The residue was subjected to column chromatography on 48 g of basic alumina eluting with 8% ethyl acetate/hexanes to afford 4.7 g (67%) of racemic tert-butyl 4-(4-(benzyloxy)phenyl)-3-oxopiperidine-1-carboxylate. LCMS (method F) RT 2.376 min, m/z 381.2 (M+); chiral SFC (method G) RT 4.54 min (46.9% AP, 4.93 min (49.7% AP). 1H NMR (400 MHz, DMSO-d6) δ 7.30-7.40 (m, 5H), 7.07 (d, J=7 Hz, 2H) 6.94 (d, J=7), 2H; 5.08 (s, 2H), 4.10 (d, J=17.6, 1H), 3.97 (d, J=17.6, 1H), 3.77 (m, 2H), 3.43 (br s, 1H), 2.16 (m, 2H), 1.42 (s, 9H).

Provenance & Evidence