반응 #47965

반응 방정식

thionyl chloride

allylmagnesium bromide

N-[3,4-difluoro-2-(4-fluorobenzoyl)phenyl]-N′-(2,2,2-trifluoroethyl)urea

5,6-difluoro-4-(4-fluorophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

triethylamine

→

4-allyl-5,6-difluoro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

용매

THF

반응 조건

후처리

1. 1
   workup.WAITAfter 30 mins at −78° C.
2. 2
   workup.WAITAfter 30 minutes at −78° C.
3. 3
   기타the reaction mixture was quenched with saturated NH4Cl
4. 4
   온도warmed to room temperature
5. 5
   추출The reaction mixture was extracted three times with EtOAc
6. 6
   세척washed with brine
7. 7
   건조The organic layer was dried over NaSO4
8. 8
   여과filtered
9. 9
   농축concentrated in vacuo
10. 10
    기타Purification by flash chromatography (1×14 cm silica gel, linear gradient 0-35% EtOAc:hexane)

실험 절차

To a solution of 5.0 g (13.289 mmol) N-[3,4-difluoro-2-(4-fluorobenzoyl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (open form) and 5,6-difluoro-4-(4-fluorophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (closed form) in 25 ml THF was added 9.261 mL (66.443 mmol) triethylamine. After 1 h at 80° C., the reaction mixture was cooled to −78° C. To this solution was added 0.969 mL (13.289 mmol) thionyl chloride. After 30 mins at −78° C., 45 mL (41.195 mmol) allylmagnesium bromide (1.0M solution in dibutyl ether) was added dropwise. After 30 minutes at −78° C., the reaction mixture was quenched with saturated NH4Cl and warmed to room temperature. The reaction mixture was extracted three times with EtOAc and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (1×14 cm silica gel, linear gradient 0-35% EtOAc:hexane) afforded 4-allyl-5,6-difluoro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one. 1H NMR (CDCl3, 400 MHz) δ 7.46 (br s, 1H, ArNHC═O); 7.42-7.40 (m, 2H, ArH); 7.10-7.00 (m, 3H, ArH); 6.44 (m, 1H, ArH); 5.73-5.66 (m, 1H, CH2CH═CH2); 5.13-5.09 (m, 2H, CH2CH═CH2); 3.73 (m, 2H, NCH2CF3); 3.15 (m, 2H, CH2CH═CH2). HRMS (ES) exact mass calcd for C19H14F6N2O: 401.1083, Found: 401.1075.

출처