تفاعل #172114

معادلة التفاعل

tri(o-tolyl)phosphine

(Trimethylsilyl)diazomethane

methyl 2-bromo-5-chlorobenzoate

acrylonitrile

sodium acetate

→

title compound

(E)-Methyl 5-chloro-2-(2-cyanovinyl)benzoate

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe mixture was heated at 120° C. for 24 hours
2. 2
   أخرىN,N-Dimethylformamide was removed in vacuo
3. 3
   أخرىthe remaining mixture was quenched with 1 N HCl(aq)
4. 4
   استخلاصextracted with ethyl acetate
5. 5
   تركيزThe ethyl acetate extracts were concentrated
6. 6
   workup.DISSOLUTIONthe residue was dissolved in 1:1 dichloromethane
7. 7
   أخرىthe mixture was quenched with acetic acid
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   أخرىpurified by silica gel column chromatography
10. 10
    غسيلeluting with 2:1 hexanes

الإجراء التجريبي

To an N,N-dimethylformamide solution (100 mL) of methyl 2-bromo-5-chlorobenzoate (25, 100 mmol) was added palladium(II) acetate (480 mg, 2.1 mmol) tri(o-tolyl)phosphine (1.2 g, 3.9 mmol), acrylonitrile (6 g, 113 mmol), and anhydrous sodium acetate (10 g, 122 mmol). The mixture was heated at 120° C. Additional palladium(II) acetate (224 mg, 1 mmol) and tri(o-tolyl)phosphine (600 mg, 2 mmol) were added, after 36 hours. The mixture was heated at 120° C. for 24 hours. N,N-Dimethylformamide was removed in vacuo and the remaining mixture was quenched with 1 N HCl(aq) and extracted with ethyl acetate. The ethyl acetate extracts were concentrated and the residue was dissolved in 1:1 dichloromethane:methanol (50 mL). (Trimethylsilyl)diazomethane (30 mL, 2 N in diethyl ether, 60 mmol) was added dropwise. After stirring overnight, the mixture was quenched with acetic acid, concentrated under reduced pressure and purified by silica gel column chromatography eluting with 2:1 hexanes:ethyl acetate to afford the title compound (2:1 E/Z isomers). 1H NMR (E isomer, Example 45A, 300 MHz, DMSO-d6) δ ppm 8.08 (d, J=16.2 Hz, 1H), 7.91 (d, J=2.1 HZ, 1H), 7.84 (d, J=8.7 HZ, 1H), 7.78 (dd, J=2.1, 8.4 Hz, 1H), 6.45 (d, J=16.5 Hz, 1H), and 3.88 (s, 3H).

المصدر