1,8-Diazabicyclo(5.4.0)undec-7-ene → (4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

To a solution of N-((4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (1i, 8.58 g, 17.98 mmol) in MeOH (50 mL) was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (3.22 ml, 21.57 mmol) and the resulting mixture was heated at 65° C. for 5 h. The reaction went to completion. The mixture was concentrated, diluted with EtOAc, washed with water, saturated NH4Cl solution, dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using a gradient of 0-20% EtOAc/hexanes to afford a white solid as (4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (5.43 g, 14.55 mmol, 81% yield). MS m/z=374.9 [M+H]+. Calculated for C12H10BrF5N2O: 373.1

1. concentrationThe mixture was concentrated
2. additiondiluted with EtOAc
3. washwashed with water, saturated NH4Cl solution
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customchromatographed on silica gel using a gradient of 0-20% EtOAc/hexanes

ORD-Eintrag

ord-9a2395cb11494e8cb2dab482fae254f9

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09296734B2