반응 #474364

반응 방정식

N-(2-Bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea

triethylamine

tris-(o-tolyl)phosphine

methyl acrylate

→

methyl {8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate

용매

Water

isobutyronitrile

반응 조건

후처리

1. 1
   온도cooled to room temperature
2. 2
   workup.STIRRINGthe mixture is stirred at room temperature for 1 h
3. 3
   여과filtered off with suction
4. 4
   세척washed with water/methanol (1:1, 300 ml) and acetonitrile (100 ml)
5. 5
   기타The residue is dried overnight at 45° C. in the VDO

실험 절차

N-(2-Bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea (300 g) is suspended in isobutyronitrile (1.2 l) under a nitrogen atmosphere, then triethylamine (210 ml), bis(acetonitrile)dichloropalladium (7.5 g), tris-(o-tolyl)phosphine (18.0 g) and methyl acrylate (210 ml) are added in this sequence. The resulting suspension is stirred under reflux (ca. 102° C.) for 16 h and then cooled to room temperature. Water (1.2 l) is added and the mixture is stirred at room temperature for 1 h, then filtered off with suction and washed with water/methanol (1:1, 300 ml) and acetonitrile (100 ml). The residue is dried overnight at 45° C. in the VDO using entraining nitrogen. A total of 208 g of methyl {8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate are obtained as a solid, corresponding to 68.5% of theory.

출처