Water → 4-Fluoro-N-{[2-oxo-6-(2-oxopyrrolidin-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

HRID 1878020Notes

Reaction equation

HRID 1878020 reaction equation
[F:1][C:2]1[CH:41]=[CH:40][C:5]([C:6]([NH:8][CH2:9][C:10]2([C:36]([F:39])([F:38])[F:37])[C:15]3[CH:16]=[C:17]([N:20]4[CH2:24][CH2:23][CH2:22][C:21]4=[O:25])[CH:18]=[CH:19][C:14]=3[N:13](CC3C=CC(OC)=CC=3)[C:12](=[O:35])[O:11]2)=[O:7])=[CH:4][CH:3]=1.[Cl-].[Cl-].[Cl-].[Al+3].O>C1(OC)C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:8][CH2:9][C:10]2([C:36]([F:37])([F:38])[F:39])[C:15]3[CH:16]=[C:17]([N:20]4[CH2:24][CH2:23][CH2:22][C:21]4=[O:25])[CH:18]=[CH:19][C:14]=3[NH:13][C:12](=[O:35])[O:11]2)=[O:7])=[CH:40][CH:41]=1

Participants

6

Reactant 3

HCID 962WaterHCID 6451240Aluminum(III) ChlorideHCID 684849574-fluoro-N-{[1-(4-methoxybenzyl)-2-oxo-6-(2-oxopyrrolidin-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

Product 1

HCID 252547244-Fluoro-N-{[2-oxo-6-(2-oxopyrrolidin-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

Reagents, catalysts & solvents 2

HCID 7519AnisoleSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Fluoro-N-{[1-(4-methoxybenzyl)-2-oxo-6-(2-oxopyrrolidin-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide (30 mg, 0.0525 mmol), aluminum trichloride (70 mg, 0.525 mmol) were mixed in anisole (0.5 mL), and the mixture was stirred at room temperature. After all the ingredients were dissolved, the temperature of the solution was raised to 100° C. and the solution was stirred for 4 hours. The temperature of the solution was brought to room temperature and the solution was diluted with ethyl acetate and then water was added thereto. Then, the organic layer was separated and washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/0), and a crude product was crystallized from ethyl acetate-diisopropyl ether, whereby the objective compound (10.1 mg, 43%) was obtained as a pale yellow solid.

Workup

  1. dissolutionAfter all the ingredients were dissolved
  2. temperaturethe temperature of the solution was raised to 100° C.
  3. stirringthe solution was stirred for 4 hours
  4. customwas brought to room temperature
  5. customThen, the organic layer was separated
  6. washwashed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. customAfter the drying agent was removed by filtration
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/0)
  11. customa crude product was crystallized from ethyl acetate-diisopropyl ether, whereby the objective compound (10.1 mg, 43%)
  12. customwas obtained as a pale yellow solid

Sources & evidence

ORD record
ord-6ca56a14d38e44edbbf1350767b582c1
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

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