تفاعل #87934

معادلة التفاعل

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

ظروف التفاعل

المعالجة

1. 1
   أخرىto crystallize from the reaction mixture
2. 2
   workup.ADDITIONDiisopropylether and dichloromethane are added
3. 3
   أخرىfurther crystals are collected
4. 4
   أخرىFurther purification
5. 5
   أخرىis performed by recrystallization from methanol and by flash chromatography on silica (dichloromethane/methanol 99:1)
6. 6
   أخرى0.68 min (X012_S02)

الإجراء التجريبي

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).

المصدر