Sodium hydride → 2-[4-[N-(tert-butoxycarbonyl)-N-methylamino]-3-fluorophenyl]-6,8-difluoro-5-(5-hexenylamino)-4H-1-benzopyran-4-one

HRID 1736149Notes

Reaction equation

HRID 1736149 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:28])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH3:19])=[C:14]([F:27])[CH:13]=3)[O:11][C:6]=2[C:5]([F:29])=[CH:4][C:3]=1[F:30].[H-].[Na+].Br[CH2:34][CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39].[Cl-].[NH4+]>CN(C)C=O>[C:23]([O:22][C:20]([N:18]([C:15]1[CH:16]=[CH:17][C:12]([C:10]2[O:11][C:6]3[C:5]([F:29])=[CH:4][C:3]([F:30])=[C:2]([NH:1][CH2:39][CH2:38][CH2:37][CH2:36][CH:35]=[CH2:34])[C:7]=3[C:8](=[O:28])[CH:9]=2)=[CH:13][C:14]=1[F:27])[CH3:19])=[O:21])([CH3:24])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 759066-Bromo-1-hexene2×HCID 19434922HCID 19434922, compound

Product 1

HCID 194349052-[4-[N-(tert-butoxycarbonyl)-N-methylamino]-3-fluorophenyl]-6,8-difluoro-5-(5-hexenylamino)-4H-1-benzopyran-4-oneYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

828 mg (1.97 mmol) of 5-amino-2-[4-[N-(tert-butoxycarbonyl)-N-methylamino]-3-fluorophenyl]-6,8-difluoro-4H-1-benzopyran-4-one obtained in Example 76 was dissolved in 40 ml of dimethylformamide under argon atmosphere, 160 mg of sodium hydride (60% oil dispersion) and 0.53 ml of 6-bromo-1-hexene were added under ice-cooling and the mixture was stirred at room temperature for 2 hours. Additional 80 mg of sodium hydride (60% oil dispersion) and 0.27 ml of 6-bromo-1-hexene were added and the mixture was stirred for additional 1.5 hours. Art aqueous saturated solution of ammonium chloride was added to the reaction solution and the mixture was extracted three times with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=8:1) to give 315 mg (32%) of 2-[4-[N-(tert-butoxycarbonyl)-N-methylamino]-3-fluorophenyl]-6,8-difluoro-5-(5-hexenylamino)-4H-1-benzopyran-4-one.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for additional 1.5 hours
  3. extractionthe mixture was extracted three times with ethyl acetate
  4. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=8:1)

Sources & evidence

ORD record
ord-f4ea68f116ad4c7d9cf5f3cbfc2fd915
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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