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

HRID 906345Notes

Reaction equation

HRID 906345 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-f676119bee324c9e9115508f815ed00a
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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