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

HRID 1192650Notes

Reaction equation

HRID 1192650 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

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 46738037tert-Butyl 4-acetamidopiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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.

Workup

  1. washwashed with water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe resulted residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-901a69d9df2e4a329fafaf8d9885e52b
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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