Methyl Acrylate → 4-QuinazolineAcetic Acid 8-Fluoro-1,2,3,4-Tetrahydro-3-[2-Methoxy-5-(TrifluoroMethyl)Phenyl]-2-Oxo-Methyl ester

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Reaction Conditions

Reaction Steps

N-(2-Bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea (2.5 kg) is suspended in isobutyronitrile under a nitrogen atmosphere (9 l), then triethylamine (1.31 kg), bis(acetonitrile)dichloropalladium (64.9 g), tris(o-tolyl)phosphine (149 g) and methyl acrylate (1.59 kg) are added in this sequence. The resulting suspension is stirred at 90-100° C. for 22 h, then cooled to room temperature. Water (9 l) is added and the mixture is stirred at room temperature for 1 h, then the solid is filtered off with suction and washed with water/methanol (1:1, 2.5 l) and acetonitrile (850 ml). The residue is dried overnight at 45° C. in the VDO to constant mass (21 h) using entraining nitrogen. A total of 1.90 kg 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 74.9% of theory.

Provenance & Evidence