4-Methylmorpholine → 2-methoxy-N-(3-nitro-5-(trifluoromethyl)phenyl)acetamide

HRID 2200139Notes

Reaction equation

HRID 2200139 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[NH2:7])([O-:3])=[O:2].[CH3:15][O:16][CH2:17][C:18](O)=[O:19].ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.O>[CH3:15][O:16][CH2:17][C:18]([NH:7][C:6]1[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[O:19]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 12251Methoxyacetic AcidHCID 757711-HydroxybenzotriazoleHCID 27757093-Nitro-5-(trifluoromethyl)aniline

Product 1

HCID 900201822-methoxy-N-(3-nitro-5-(trifluoromethyl)phenyl)acetamideYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Stir the mixture of 3-nitro-5-(trifluoromethyl)aniline (500 mg, 2.4 mmol), 2-methoxyacetic acid (220 mg, 2.4 mmol), 1-hydroxybenzotriazole (HOBt, 324 mg, 2.4 mmol), N-methyl morpholine (NMM, 480 mg, 4.8 mmol), 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (EDCI.HCl, 920 mg, 4.8 mmol) in DMF (8 mL) at 80° C. for 16 hrs. Cool the reaction mixture to room temperature, add water (100 mL), extract with ethyl acetate (30 mL×2), combine the organic layers, wash with brine, dry over anhydrous sodium sulfate, and concentrate under reduced pressure to give the crude product. Purify by flash chromatography (silica gel, EtOAc:PE=15:85) to yield the target compound (260 mg, 39%).

Workup

  1. extractionextract with ethyl acetate (30 mL×2)
  2. washwash with brine
  3. dry with materialdry over anhydrous sodium sulfate
  4. concentrationconcentrate under reduced pressure
  5. customto give the crude product
  6. customPurify by flash chromatography (silica gel, EtOAc:PE=15:85)

Sources & evidence

ORD record
ord-25fcfd6815c647c0a238d86d18a350e3
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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