Sodium Hydroxide → HCID 86607897, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (3S,4R)-1-tert-butyl 3-methyl 4-(4-(benzyloxy)phenylsulfonamido)-3-methylpiperidine-1,3-dicarboxylate (4.494 g, 8.67 mmol), 5 M NaOH (10 mL), and THF (20 mL) was added methanol until the reaction became homogeneous. The solution was stirred at 45° C. overnight, then diluted with pH 4 NaH2PO4 (aq) and extracted with ethyl acetate (3×). Combined organic extracts were dried over Na2SO4 and concentrated to give an orange solid. The solid was then combined with benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) (4.766 g, 10.78 mmol), O-tert-butylhydroxylamine hydrochloride (2.442 g, 19.28 mmol), triethylamine (5.4 mL), and DMF (10 mL) and the reaction mixture was stirred overnight at room temperature. The mixture was then diluted with brine and extracted with ethyl acetate (3×). The combined organic extracts were dried over Na2SO4 and purified via column chromatography on silica gel eluting with 30% ethyl acetate/hexanes to give (3S,4R)-tert-butyl 4-(4-(benzyloxy)phenylsulfonamido)-3-(tert-butoxycarbamoyl)-3-methylpiperidine-1-carboxylate (4.659 g, 8.09 mmol, 93%) as a colorless solid. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.09 (s, 3H) 1.23-1.25 (m, 9H) 1.40-1.51 (m, 10H) 1.57-1.60 (m, 3H) 1.65-1.72 (m, 1H) 2.49 (d, J=15.16 Hz, 1H) 2.72-2.83 (m, 1H) 3.16 (ddd, J=12.38, 8.72, 3.92 Hz, 1H) 3.98 (dt, J=13.58, 2.31 Hz, 1H) 4.31 (d, J=14.65 Hz, 1H) 5.11 (s, 2H) 7.01 (ddd, J=9.41, 2.78, 2.46 Hz, 2H) 7.33-7.44 (m, 5H) 7.78-7.82 (m, 2H).

Provenance & Evidence