Réaction #87934

Équation de réaction

3-Bromo-4-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzonitrile

carbon monoxide

sodium acetate

methanol

INTERMEDIATE 23

3-Bromo-4-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzonitrile

→

5-Cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid methyl ester

Conditions de réaction

Traitement

1. 1
   Autreto crystallize from the reaction mixture
2. 2
   workup.ADDITIONDiisopropylether and dichloromethane are added
3. 3
   Autrefurther crystals are collected
4. 4
   AutreFurther purification
5. 5
   Autreis performed by recrystallization from methanol and by flash chromatography on silica (dichloromethane/methanol 99:1)
6. 6
   Autre0.68 min (X012_S02)

Mode opératoire

3-Bromo-4-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzonitrile (INTERMEDIATE 23, 10.5 g, 20.8 mmol), 1.1-bis(diphenylphosphino)-ferrocen (1.15 g, 2.08 mmol), palladium acetate (233 mg, 1.04 mmol) and sodium acetate (5.12 g, 62.5 mmol) are suspended in methanol (180 mL) and treated with carbon monoxide at 5 bar and 100° C. for 40 h. The product begins to crystallize from the reaction mixture. Diisopropylether and dichloromethane are added and further crystals are collected. Further purification is performed by recrystallization from methanol and by flash chromatography on silica (dichloromethane/methanol 99:1). Yield: 1.7 g. ESI mass spectrum: [M+H]+=484; Retention time HPLC: 0.68 min (X012_S02).

Source