Water → 2-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl]-6,8-difluoro-5-(4-methyl-3-pentenylamino)-4H-1-benzopyran-4-one

HRID 1736214Notes

Reaction equation

HRID 1736214 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:30])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:19][O:20][CH3:21])=[C:14]([F:29])[CH:13]=3)[O:11][C:6]=2[C:5]([F:31])=[CH:4][C:3]=1[F:32].[H-].[Na+].Br[CH2:36][CH2:37][CH:38]=[C:39]([CH3:41])[CH3:40].O>CN(C)C=O>[C:25]([O:24][C:22]([N:18]([C:15]1[CH:16]=[CH:17][C:12]([C:10]2[O:11][C:6]3[C:5]([F:31])=[CH:4][C:3]([F:32])=[C:2]([NH:1][CH2:36][CH2:37][CH:38]=[C:39]([CH3:41])[CH3:40])[C:7]=3[C:8](=[O:30])[CH:9]=2)=[CH:13][C:14]=1[F:29])[CH2:19][O:20][CH3:21])=[O:23])([CH3:27])([CH3:28])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1375215-Bromo-2-methyl-2-penteneHCID 194347945-amino-2-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl)-6,8-difluoro-4H-1-benzopyran-4-one

Product 1

HCID 194348222-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl]-6,8-difluoro-5-(4-methyl-3-pentenylamino)-4H-1-benzopyran-4-oneYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.70 g (6.00 mmol) of the above 5-amino-2-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl]-6,8-difluoro-4H-1-benzopyran-4-one was dissolved in 60 mL of dimethylformamide under argon atmosphere, 480 mg (12.0 mmol) of sodium hydride (60% oil dispersion) and 4.0 mL (30 mmol) of 5-bromo-2-methyl-2-pentene were added under ice-cooling and the mixture was stirred at room temperature for 18 hours. The reaction solution was cooled on ice, water was added and the mixture was extracted twice with ethyl acetate. The organic layer was washed twice with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:acetonitrile=30:1) to give 1.21 g of 2-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl]-6,8-difluoro-5-(4-methyl-3-pentenylamino)-4H-1-benzopyran-4-one (yield: 38%).

Workup

  1. temperaturecooling
  2. additionwas added
  3. extractionthe mixture was extracted twice with ethyl acetate
  4. washThe organic layer was washed twice with water and once 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 (chloroform:acetonitrile=30:1)

Sources & evidence

ORD record
ord-0f3834f2211e4c9288cc60c83e5f763c
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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