Hydroxyamine hydrochloride → 8-(2-Chlorophenylamino)-6,7-difluoro-4-methylbenzo[d][1,2]oxazin-1-one

HRID 1723684Notes

Reaction equation

HRID 1723684 reaction equation
[C:1]([C:4]1[C:9]([C:10]([OH:12])=[O:11])=[C:8]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:20])[C:7]([F:21])=[C:6]([F:22])[CH:5]=1)(=O)[CH3:2].Cl.[NH2:24]O>CO.O.CCOC(C)=O>[Cl:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[NH:13][C:8]1[C:9]2[C:10](=[O:11])[O:12][N:24]=[C:1]([CH3:2])[C:4]=2[CH:5]=[C:6]([F:22])[C:7]=1[F:21]

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 860527646-Acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid

Product 1

HCID 674037018-(2-Chlorophenylamino)-6,7-difluoro-4-methylbenzo[d][1,2]oxazin-1-oneYield 55.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of 6-acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid (50 mg, 0.15 mmol) and hydroxylamine hydrochloride (11 mg, 0.15 mmol) in MeOH-H2O (1 mL/0.5 mL) was added TEA (0.022 mL, 0.15 mmol) at room temperature. The resulting mixture was stirred for 16 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give the crude material that was purified by silica gel flash column chromatography (100% CH2Cl2) to afford the desired product (26.8 mg, 54%).

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude material that
  6. customwas purified by silica gel flash column chromatography (100% CH2Cl2)

Sources & evidence

ORD record
ord-49c94779d7d044d3a62c04cb7b7c7e49
Source dataset
uspto-grants-2009_02
Patent number
US07485643B2

Reaction notes

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