Pyridine → N-[(1-t-Butoxycarbonyl-4-phenylpiperidin-4-yl)methyl]acetamide

HRID 1419564Notes

Reaction equation

HRID 1419564 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][CH2:9][C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.N1C=CC=CC=1>ClCCl>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][C:10]([CH2:9][NH:8][C:1](=[O:3])[CH3:2])([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:11][CH2:12]1)=[O:17])([CH3:21])([CH3:22])[CH3:20]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 10565452Tert-butyl 4-(aminomethyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 58117727N-[(1-t-Butoxycarbonyl-4-phenylpiperidin-4-yl)methyl]acetamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetic anhydride (2.59 mL, 2.81 g, 27.5 mmol) was added dropwise to a stirred, cooled (0° C.) solution of 4-aminomethyl-1-t-butoxycarbonyl-4-phenylpiperidine (7.96 g) and pyridine (3.03 mL, 2.97 g, 37.5 mmol) in dichloromethane (100 mL) and the mixture was stirred at room temperature for 18 h. The solvent was evaporated under reduced pressure, aqueous sodium hydrogen carbonate (saturated, 100 mL) was added and the mixture was extracted with ethyl acetate (3×100 mL). The combined organic fractions were washed with aqueous citric acid (10%, 2×100 mL), aqueous sodium hydrogen carbonate (saturated, 100 mL) and brine (100 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/hexane (50:50 increasing to 100:0) to give the title compound as an off-white solid (5.96 g, 72% from 4-cyano-4-phenylpiperidine hydrochloride), δH (250 MHz, CDCl3) 7.45-7.26 (5H, m), 5.00 (1H, br m), 3.67 (2H, m), 3.45 (2H, br m), 3.21 (2H, m), 2.08 (2H, m), 1.88 (3H, s), 1.78 (2H, m), and 1.43 (9H, s).

Workup

  1. customThe solvent was evaporated under reduced pressure, aqueous sodium hydrogen carbonate (saturated, 100 mL)
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
  4. washThe combined organic fractions were washed with aqueous citric acid (10%, 2×100 mL), aqueous sodium hydrogen carbonate (saturated, 100 mL) and brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with ethyl acetate/hexane (50:50 increasing to 100:0)

Sources & evidence

ORD record
ord-c73892abe6654feabac08dec510d9b6a
Source dataset
uspto-grants-1999_03
Patent number
US05885999

Reaction notes

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