Methyl iodide → (RS)-2-(5,6-Difluoro-1-methyl-1H-benzoimidazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1367004Notes

Reaction equation

HRID 1367004 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]1[CH2:16][C:17]1[NH:21][C:20]2[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:19]=2[N:18]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].I[CH3:29]>CN(C)C=O.O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]1[CH2:16][C:17]1[N:18]([CH3:29])[C:19]2[CH:25]=[C:24]([F:26])[C:23]([F:27])=[CH:22][C:20]=2[N:21]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 6328Methyl iodide3×HCID 24758Sodium hydride2×HCID 66968258(RS)-2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66968213(RS)-2-(5,6-Difluoro-1-methyl-1H-benzoimidazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of sodium hydride (0.46 g, 60% dispersion in mineral oil) in dimethylformamide (30 ml) at 0° C., under argon, was added (RS)-2-(5,6-difluoro-1H-benzoimidazol-2-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester, D59 (2 g) and the reaction mixture stirred for a further 30 min. before the addition of iodomethane (0.78 ml). The reaction mixture was then stirred at room temperature for 18 h, a further equivalent of iodomethane (0.35 ml) was added and stirring continued for 24 h. Further portions of sodium hydride (0.23 g, 60% dispersion in mineral oil) and iodomethane (0.35 ml) were added and the reaction stirred for an additional 24 h. After diluting with water, the aqueous layer was extracted with diethyl ether (3×). The combined organics were dried (MgSO4) and solvent removed in vacuo to afford the title compound (0.5 g).

Workup

  1. stirringstirring
  2. waitcontinued for 24 h
  3. stirringthe reaction stirred for an additional 24 h
  4. extractionthe aqueous layer was extracted with diethyl ether (3×)
  5. dry with materialThe combined organics were dried (MgSO4) and solvent
  6. customremoved in vacuo

Sources & evidence

ORD record
ord-2aeb662529414420b7c03dbf652fac12
Source dataset
uspto-grants-2011_02
Patent number
US07893090B2

Reaction notes

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