تفاعل #1908187

معادلة التفاعل

N,N-dicyclohexylmethylamine

tert-butyl acrylate

2-(3-cyano-4-isopropyloxyphenyl)-5-(4-bromo-2-methyphenyl)-1,3,4-thiadiazole

2-(di-tert-butylphosphino)biphenyl

→

tert-Butyl 3-(4-(5-(3-Cyano-4-isopropyloxyphenyl)-1,2,4-thiadiazol-3-yl)-3-methylphenyl)-2-propenoate

المذيبات

dioxane

EtOAc

dioxane

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solution was degassed with argon
2. 2
   ترشيحfiltered trough a disposable frit
3. 3
   تركيزconcentrated
4. 4
   أخرىPure product was isolated by a column chromatography

الإجراء التجريبي

In an oven-dried flask, under an atmosphere of argon, 10 mg of 2-(di-tert-butylphosphino)biphenyl (0.03 mmol) and 13 mg of tris(dibenzylideneacetone)-dipalladium-chloroform complex (0.015 mmol) were dissolved in 10 mL of anhydrous dioxane and the solution was degassed with argon. To this mixture, 100 μL of N,N-dicyclohexylmethylamine (0.45 mmol), 55 μL of tert-butyl acrylate (0.38 mmol), and a dioxane (1 mL) solution of 125 mg (0.30 mmol) of 2-(3-cyano-4-isopropyloxyphenyl)-5-(4-bromo-2-methyphenyl)-1,3,4-thiadiazole (from Step B) were added sequentially via syringe. The resulting mixture was heated under argon atmosphere at 95° C. for 2 h. The reaction mixture was diluted with 20 mL of EtOAc, filtered trough a disposable frit and concentrated. Pure product was isolated by a column chromatography, using Biotage 40S column (eluent: hexanes/EtOAc=4/1) as a mixture of (E)- and (Z)-stereoisomers: 1H NMR (500 MHZ, CDCl3, major, (E)-stereoisomer) δ 1.46 (d, J=6.5, 6H), 2.69 (s, 3H), 4.79 (sep, J=6.5, 1H), 6.47 (d, J=15.5, 1H), 7.12 (d, J=9.0, 1H), 7.51 (d, J=9.0, 1H), 7.52 (s, 1H), 7.61 (d, J=15.5, 1H), 7.80 (d, J=8.0, 1H), 8.18 (d, J=2.0, 1H), 8.25 (dd, J=8.0, 2.0, 1H).

المصدر