Acetic Anhydride → tert-Butyl 4-acetamidopiperidine-1-carboxylate

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[C:15](OC(=O)C)(=[O:17])[CH3:16].C(N(CC)CC)C>C(Cl)Cl>[C:15]([NH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)(=[O:17])[CH3:16]

Participants

Procedure

tert-Butyl 4-aminopiperidine-1-carboxylate (0.10 g, 0.50 mmol) was combined with acetic anhydride (0.052 mL, 0.55 mmol) and triethylamine (0.21 mL, 1.5 mmol) in methylene chloride (2 mL) at room temperature and stirred for 2 hours. The reaction was diluted with dichloromethane, washed with water, dried over MgSO4 and concentrated. The resulted residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane) to give tert-butyl 4-(acetylamino)piperidine-1-carboxylate, LCMS [M+Na]+: m/z=265.1. The later was treated with 4.57 M hydrogen chloride in 1,4-dioxane (1 mL, 4 mmol) at room temperature for 1 hour. The mixture was concentrated to give crude HCl salt product (0.057 g), which was used directly in the next step. LCMS calculated for C7H15N2O (M+H)+: m/z=143.1; Found: 143.1.