Methyl Methanesulfonate → N-methyl-N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)trifluoroacetamide

HRID 1978343Notes

Reaction equation

HRID 1978343 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:24]S(OC)(=O)=O.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:24][N:17]([CH2:16][CH:13]1[CH2:14][CH2:15][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[CH2:11][CH2:12]1)[C:18](=[O:23])[C:19]([F:20])([F:21])[F:22]

Participants

6

Reactant 4

HCID 4156Methyl MethanesulfonateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 21994020N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)trifluoroacetamide

Product 1

HCID 21994204N-methyl-N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)trifluoroacetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under nitrogen, 0.21 g (5.25 mM) of 60% sodium hydride-liquid paraffin was added to a solution of 1.51 g (4.87 mM) of N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)trifluoroacetamide in N,N-dimethylformamide (10 ml) at 0° C. and the mixture was stirred at the prevailing temperature for 40 minutes. To this reaction mixture was added 0.5 ml (5.90 mM) of methyl methanesulfonate and the mixture was stirred at room temperature for 112 hours. The mixture was further stirred at 100° C. for 2.5 hours, at the end of which time the reaction was stopped by adding saturated aqueous solution of sodium hydrogen carbonate. The reaction mixture was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4. The crude product thus obtained was purified by column chromatography (ethyl acetate-hexane 40%) to provide the title compound.

Workup

  1. stirringthe mixture was stirred at room temperature for 112 hours
  2. stirringThe mixture was further stirred at 100° C. for 2.5 hours, at the end of which time the reaction
  3. extractionThe reaction mixture was then extracted with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous solution of sodium chloride
  5. dry with materialdried over MgSO4
  6. customThe crude product thus obtained
  7. customwas purified by column chromatography (ethyl acetate-hexane 40%)

Sources & evidence

ORD record
ord-26f4ce169ab544a38ec3175e834da75e
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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