3-(Trifluoromethyl)benzeneacetic acid → N-methoxy-N-methyl-2-[3-(trifluoromethyl)phenyl]acetamide

HRID 491398Notes

Reaction equation

HRID 491398 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([CH2:9][C:10](O)=[O:11])[CH:6]=[CH:7][CH:8]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH3:47][NH:48][O:49][CH3:50]>CN(C=O)C.C(OCC)(=O)C>[CH3:50][O:49][N:48]([CH3:47])[C:10](=[O:11])[CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:14])([F:13])[F:1])[CH:4]=1

Participants

8

Reactant 5

HCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 22712418N-methoxy-N-methyl-2-[3-(trifluoromethyl)phenyl]acetamideYield 73.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(trifluoromethyl)phenylacetic acid (1.00 g, TCI) in DMF (15 ml) was added with WSC HCl (1.28 g, KOKUSAN), HOBT (794 mg, KOKUSAN), and DIEA (1.02 ml, ALD), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was added with a solution of N,O-dimethylhydroxylamine hydrochloride (956 mg, WAKO) in DMF (5 ml) added with DIEA (1.74 ml) and stirred for 20 minutes at room temperature beforehand, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was added with ethyl acetate (150 ml), successively washed with 1 N aqueous hydrochloric acid, purified water, saturated aqueous sodium hydrogencarbonate, and saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain the title compound (Intermediate pa-01, 893 mg).

Workup

  1. stirringstirred for 20 minutes at room temperature beforehand
  2. stirringthe mixture was stirred at room temperature for 16 hours
  3. washsuccessively washed with 1 N aqueous hydrochloric acid
  4. custompurified water, saturated aqueous sodium hydrogencarbonate, and saturated brine
  5. customdried
  6. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-1544de69157a49d6a0fa8b41943599a5
Source dataset
uspto-grants-2009_05
Patent number
US07531533B2

Reaction notes

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