Water → N-methoxy-N-methyl-1-(tert-butoxycarbonyl)-4-fluoropiperidine-4-carboxamide

HRID 606183Notes

Reaction equation

HRID 606183 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:17])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:31][NH:32][O:33][CH3:34].O>ClCCl.C(OCC)(=O)C>[CH3:34][O:33][N:32]([CH3:31])[C:14]([C:11]1([F:17])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:16]

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 210503971-(tert-Butoxycarbonyl)-4-fluoropiperidine-4-carboxylic Acid

Product 1

HCID 22248582N-methoxy-N-methyl-1-(tert-butoxycarbonyl)-4-fluoropiperidine-4-carboxamideYield 90.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 2.19 g of 1-(tert-butoxycarbonyl)-4-fluoropiperidine-4-carboxylic acid in 30 ml of dichloromethane, 2.16 g of 1,1′-carbonyldiimidazole was added and the mixture was stirred at room temperature for 1.5 hours. Next, 1.30 g of N-methyl-O-methylhydroxylamine hydrochloride was added and the mixture was stirred overnight at room temperature. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with aqueous sodium carbonate solution, water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (2.33 g, 90% yield).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred overnight at room temperature
  3. washThe organic layer was washed with aqueous sodium carbonate solution, water and saturated brine in that order
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-485bff0933a440169ba870f5b4305600
Source dataset
uspto-grants-2011_03
Patent number
US07915274B2

Reaction notes

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