Acetic Acid → 2-{[2,2-difluoro-2-(3-butoxyphenyl)-ethyl]-methylamino}-N,N-dimethyl-acetamide

HRID 62595Notes

Reaction equation

HRID 62595 reaction equation
[F:1][C:2]([F:22])([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:12]=1)[CH2:3][NH:4][CH2:5][C:6]([N:8]([CH3:10])[CH3:9])=[O:7].C=O.[C:25](O)(=O)C>C1COCC1>[F:1][C:2]([F:22])([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:12]=1)[CH2:3][N:4]([CH3:25])[CH2:5][C:6]([N:8]([CH3:10])[CH3:9])=[O:7]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 712FormaldehydeHCID 711522752-[2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethyl-acetamide

Product 1

HCID 711520642-{[2,2-difluoro-2-(3-butoxyphenyl)-ethyl]-methylamino}-N,N-dimethyl-acetamideYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

107.5 mg (0.34 mmol) of the free base of 2-[2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethyl-acetamide (see Example 1-1) are dissolved in dry THF (10 mL). To this solution, formaldehyde (36.5% water solution, 52.1 μL; 0.69 mmol), acetic acid (2.5 mL), and MP-CNBH3 (2.3 mmol/g; 325 mg; 0.75 mmol) are added sequentially. After stirring 1 hour the reaction is completed. After further stirring for 1.5 hours, the reaction mixture is evaporated. The crude residue is flash-chromatographed on silica gel using DCM/MeOH (99.5/0.5) as an eluant. 73.1 mg (65%) of pale yellow fluid 2-{[2,2-difluoro-2-(3-butoxyphenyl)-ethyl]-methylamino}-N,N-dimethyl-acetamide are obtained.

Workup

  1. stirringAfter further stirring for 1.5 hours
  2. customthe reaction mixture is evaporated
  3. customThe crude residue is flash-chromatographed on silica gel

Sources & evidence

ORD record
ord-6e02c5f41c6f4d259272efc05125ecbd
Source dataset
uspto-grants-2016_09
Patent number
US09447029B2

Reaction notes

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