Water → 3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorobenzoic acid

温度

90 °C

To a mixture of N-((4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (2.19 g, 4.59 mmol), bis(tri-t-butylphosphine)palladium(0) (0.23 g, 0.46 mmol), xantphos (0.53 g, 0.92 mmol), potassium carbonate (1.90 g, 13.76 mmol) in DMF (15 mL) and water (0.83 ml, 45.9 mmol) was bubbled CO gas for 10 min. The mixture was heated at 90° C. for 4 h, then was allowed to cool to rt. 1N HCl was added until pH˜4. Water was then added and a precipitate was formed. The solid was filtered, washed with water, and dried. The filtrate was concentrated in vacuo. The crude product was purified by silica gel chromatographed, eluting with a gradient of 1% to 8% MeOH in 0.5% AcOH/DCM, to provide the acid as a white solid (0.44 g, 21.45% yield). MS m/z=443 [M+H]+. Calculated for C20H15F5N2O4: 442.3.

1. customwas bubbled CO gas for 10 min
2. temperatureto cool to rt
3. addition1N HCl was added until pH˜4
4. additionWater was then added
5. customa precipitate was formed
6. filtrationThe solid was filtered
7. washwashed with water
8. customdried
9. concentrationThe filtrate was concentrated in vacuo
10. customThe crude product was purified by silica gel
11. customchromatographed
12. washeluting with a gradient of 1% to 8% MeOH in 0.5% AcOH/DCM

ORDレコード

ord-f9e12d561933474cbd76418e352a1544

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09296734B2