tert-Butanol → HCID 66789903, compound

HRID 1929418Notes

Reaction equation

HRID 1929418 reaction equation
C(O)(C)(C)C.Cl[C:7]1[CH:8]=[C:9]([N:14]2[C:19]3[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:18]=3[O:17][C:16]([CH3:30])([CH3:29])[C:15]2=[O:31])[CH:10]=[CH:11][C:12]=1[F:13].C(=O)([O-])[O-].[K+].[K+].[C:38](=[O:45])([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[NH2:39]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C1(B(O)O)C=CC=CC=1>[CH3:29][C:16]1([CH3:30])[C:15](=[O:31])[N:14]([C:9]2[CH:10]=[CH:11][C:12]([F:13])=[C:7]([NH:39][C:38](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH:8]=2)[C:19]2[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:18]=2[O:17]1

Participants

9

Reactant 4

HCID 6386tert-Butanol2×HCID 11430Potassium Carbonate2×HCID 77922tert-Butyl carbamate2×HCID 24744482HCID 24744482, compound

Product 1

HCID 66789903HCID 66789903, compoundYield 115.1%

Reagents, catalysts & solvents 4

HCID 66827Phenylboronic AcidCatalystHCID 167845palladium(II) acetateCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of palladium acetate (1.3 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (7.2 mg), phenylboronic acid (0.9 mg) and tert-butanol (2 mL) was stirred at room temperature for 20 minutes under argon atmosphere. To the reaction mixture were added N-[4-(3-chloro-4-fluorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide (compound obtained in Example 13, 60 mg), potassium carbonate (62 mg), tert-butyl carbamate (35 mg) and tert-butanol (5 mL), and the mixture was refluxed for 3 hours. To the reaction mixture were further added palladium acetate (1.3 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (7.2 mg), potassium carbonate (62 mg) and tert-butyl carbamate (35 mg), and the mixture was further refluxed for 20 hours. After cooling, the reaction mixture was diluted with ethyl acetate, and the mixture was washed successively with water and brine, dried over sodium sulfate and concentrated in vacuo. The resultant residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=4/1→3/7) to give tert-butyl (5-{2,2-dimethyl-7-[(methylsulfonyl)amino]-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl}-2-fluorophenyl)-carbamate (83 mg) as a colorless powder.

Workup

  1. temperaturethe mixture was refluxed for 3 hours
  2. temperaturethe mixture was further refluxed for 20 hours
  3. temperatureAfter cooling
  4. washthe mixture was washed successively with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=4/1→3/7)

Sources & evidence

ORD record
ord-9369cd8551ef442c88768fc5ccad14b5
Source dataset
uspto-grants-2012_05
Patent number
US08188073B2

Reaction notes

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