Cesium carbonate → Methyl 4-((tert-butoxycarbonyl)amino)-2,6-difluorobenzoate

HRID 56622Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]([F:12])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:13])[CH:3]=1.[C:14](=[O:21])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[NH2:15].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:17]([O:16][C:14]([NH:15][C:2]1[CH:11]=[C:10]([F:12])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:13])[CH:3]=1)=[O:21])([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 140 °C

Procedure

Under argon, a microwave vessel was charged with 54 mg (0.22 mmol) of methyl 4-bromo-2,6-difluorobenzoate, 118 mg (1.01 mmol, 4.7 eq.) of tert-butyl carbamate, 4.6 mg (0.02 mmol, 0.1 eq.) of palladium(II) acetate, 15 mg (0.026 mmol, 0.13 eq.) of Xantphos, 137 mg (0.42 mmol, 2 eq.) of caesium carbonate and 2 ml of 1,4-dioxane. A stream of argon was passed through the suspension for 2 min. The reaction mixture was heated in the microwave at 140° C. for 20 min. After filtration through kieselguhr, the filtrate was concentrated under reduced pressure. The crude product was purified by normal phase chromatography (mobile phase: dichloromethane/methanol 10-50% mixtures). Yield: 37 mg (60% of theory)

Workup

filtrationAfter filtration through kieselguhr
concentrationthe filtrate was concentrated under reduced pressure
customThe crude product was purified by normal phase chromatography (mobile phase: dichloromethane/methanol 10-50% mixtures)

Sources & evidence

ORD record: ord-b7947dd28d474c86b3456aa7c72fe693
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434690B2

Reaction notes

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