tert-Butyl 4-oxopiperidine-1-carboxylate → 1,1-Dimethylethyl 4-{[4-fluoro-3-(methyloxy)phenyl]amino}-1-piperidinecarboxylate

HRID 883766Notes

Reaction equation

HRID 883766 reaction equation
O=[C: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.[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[O:23][CH3:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)=[CH:18][C:17]=1[O:23][CH3:24]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27745334-Fluoro-3-methoxyanilineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 576995241,1-Dimethylethyl 4-{[4-fluoro-3-(methyloxy)phenyl]amino}-1-piperidinecarboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (1.41 g, 7.1 mmol) and 4-fluoro-3-methoxyaniline (1 g, 7.1 mmol) was stirred at room temperature for 1 h. Sodium tri(acetoxy)borohydride (1.95 g, 9.2 mmol) was then added and stirring continued over-weekend. The reaction mixture was diluted with DCM, washed with saturated aqueous NaHCO3 solution, dried and then concentrated in vacuo. Column chromatography eluting with 0-50% Et2O/petroleum ether gave the title compound as a white solid (1.45 g). δH (CDCl3, 400 MHz) 6.89 (1H, dd), 6.22 (1H, dd), 6.09 (1H, m), 4.03 (2H, br s), 3.84 (3H, s), 3.36 (1H, br s), 2.92 (2H, m), 2.03 (2H, m), 1.46 (9H, s), 1.32 (2H, m).

Workup

  1. waitcontinued over-weekend
  2. washwashed with saturated aqueous NaHCO3 solution
  3. customdried
  4. concentrationconcentrated in vacuo
  5. washColumn chromatography eluting with 0-50% Et2O/petroleum ether

Sources & evidence

ORD record
ord-91b238157abe4d15ab4a8548dd869177
Source dataset
uspto-grants-2012_08
Patent number
US08236953B2

Reaction notes

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