Hydrochloric Acid → 1-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone

HRID 578776

Reaction equation

HRID 578776 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])=[CH:4][C:3]=1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].Br[C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[O:29][CH3:30].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+].Cl>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[C:9]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[O:29][CH3:30])([CH3:10])[CH3:11])=[CH:4][C:3]=1[NH:13][C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1362922-Bromo-4-fluoroanisoleHCID 23676156Sodium t-butoxideHCID 44558591Tri-t-butylphosphine fluoroborateHCID 580223281-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-methyl-1-propanone

Product 1

HCID 689917521-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-[4-fluoro-3-(tert-butoxycarbonyl -amino)phenyl]-2-methyl-1-propanone (0.11 g), 2-bromo-4-fluoroanisole (0.057 mL), palladium(II) acetate (4.5 mg), tri(tert-butyl)phosphine tetrafluoroborate (5.8 mg) and sodium tert-butoxide (96 mg) in tetrahydrofuran (1 mL) was stirred at 70° C. under an argon atmosphere for 3 days. To the reaction mixture was added water, and the mixture was stirred for 10 minutes. The mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1) to give 1-[4-fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro -2-methoxyphenyl)-2-methyl-1-propanone (45 mg). This material was dissolved in hydrochloric acid (4 mol/L ethyl acetate solution, 3 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: n-hexane/ethyl acetate=4/1 -3/1) to give the title compound (25 mg).

Workup

  1. stirringthe mixture was stirred for 10 minutes
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and brine successively
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1)

Sources & evidence

ORD record
ord-8b57d600bee741c4b3bb50dc1965b622
Source dataset
uspto-grants-2015_05
Patent number
US09040693B2

Linked notes

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