Acetic Anhydride → Tert-butyl 3-acetamido-1-(4-chlorophenyl)propylcarbamate
Reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][CH2:9][CH2:10][CH:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:1]([NH:8][CH2:9][CH2:10][CH:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)(=[O:3])[CH3:2]Participants
Conditions
- Temperature
- 20 °C
Procedure
Acetic anhydride (0.084 mL, 0.89 mmol) was added dropwise to tert-butyl 3-amino-1-(4-chlorophenyl)propylcarbamate (Intermediate 25) (203 mg, 0.71 mmol) and N,N-diisopropylethylamine (0.248 mL, 1.43 mmol) in DCM (5 mL) at 20° C. The resulting solution was stirred at 20° C. for 16 hours. The reaction mixture was quenched with NaHCO3 (2M) (10 mL) and water (10 mL) and extracted with DCM (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 2.5% MeOH in DCM. Pure fractions were evaporated to dryness to afford tert-butyl 3-acetamido-1-(4-chlorophenyl)propylcarbamate (142 mg, 61.0%) as a white solid. 1H NMR (399.9 MHz, DMSO-d6) δ1.36 (9H, s), 1.67-1.82 (2H, m), 1.79 (3H, s), 2.97 (2H, q), 4.50 (1H, d), 7.32 (2H, d), 7.38 (2H, d), 7.43-7.45 (1H, m), 7.79 (1H, s). m/z (ESI+) (M+H)+=327; HPLC tR=2.03 min.
Workup
- customThe reaction mixture was quenched with NaHCO3 (2M) (10 mL) and water (10 mL)
- extractionextracted with DCM (20 mL)
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- customevaporated
- customto afford crude product
- customThe crude product was purified by flash silica chromatography, elution gradient 0 to 2.5% MeOH in DCM
- customPure fractions were evaporated to dryness
Sources & evidence
- ORD record
- ord-89d21aa609684d20bd0e02c22dd4baa8
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08101623B2
Reaction notes
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