Dimethylformamide → 4-fluoro-2-(2-fluoro-phenylamino)-N-methoxy-N-methyl-benzamide

HRID 1887809Notes

Reaction equation

HRID 1887809 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[CH:3]=1.C(N(CC)CC)C.CN(C=O)C.Cl.[CH3:32][NH:33][O:34][CH3:35]>C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:33]([O:34][CH3:35])[CH3:32])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 712089244-Fluoro-2-(2-fluoro-phenylamino)-benzoic acid

Product 1

HCID 866757674-fluoro-2-(2-fluoro-phenylamino)-N-methoxy-N-methyl-benzamideYield 85.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 500 mL round bottom flask, 4-fluoro-2-(2-fluoro-phenylamino)-benzoic acid (6.0 g, 24.1 mmol), O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluorophosphate (HBTU) (18.5 g, 48 mmol) and triethylamine (20 mL, 144 mmol) were added to DMF (80.0 mL). The reaction mixture was stirred for 1 hr. at room temperature, then N,O-dimethylhydroxylamine hydrochloride (4.7 g, 48 mmol) was added. The mixture was stirred for 2 hr. The reaction mixture was poured into 300 mL of ethyl acetate and washed with saturated ammonium chloride (2×150 mL), water (2×200 mL) and brine (1×200 mL). The organic layer was evaporated and purified by flash chromatography using 30% ethyl acetate-hexanes to give 4-fluoro-2-(2-fluoro-phenylamino)-N-methoxy-N-methyl-benzamide (6.0 g, 85.3%).

Workup

  1. stirringThe mixture was stirred for 2 hr
  2. washwashed with saturated ammonium chloride (2×150 mL), water (2×200 mL) and brine (1×200 mL)
  3. customThe organic layer was evaporated
  4. custompurified by flash chromatography

Sources & evidence

ORD record
ord-e9a2d8f022e649fc94b330dfcdab9673
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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