تفاعل #1511172

معادلة التفاعل

sodium hydrogencarbonate

compound

8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-[1-(4-chlorophenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

3-methylphenylboronic acid

tripotassium phosphate

→

product

{8-Methyl-3-[1-(3′-methylbiphenyl-4-yl)cyclopropyl]-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol

المذيبات

dioxane

water

ظروف التفاعل

المعالجة

1. 1
   استخلاصthe mixture was extracted with dichloromethane
2. 2
   غسيلthe organic layer was washed with saturated sodium chloride solution
3. 3
   تجفيفdried with anhydrous sodium sulfate
4. 4
   ترشيحAfter filtration
5. 5
   تركيزthe filtrate was concentrated under reduced pressure
6. 6
   أخرىthe residue was partially purified by silica gel chromatography (Isco Combiflash, 12 g, ethyl acetate:hexane=0:100 to 100:0, gradient)

الإجراء التجريبي

A solution of the compound (232 mg, 0.5 mmol) obtained in Example 1-2), 3-methylphenylboronic acid (105 mg, 0.77 mmol), tris(dibenzylideneacetone)dipalladium(0) (23 mg, 0.05 mmol), tricyclohexylphosphine (17 mg, 0.12 mmol), and tripotassium phosphate (186 mg, 0.85 mmol) in dioxane (2 mL) and water (1 mL) was stirred at 140° C. for 2 h under microwave irradiation. The reaction mixture was cooled to room temperature, saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was partially purified by silica gel chromatography (Isco Combiflash, 12 g, ethyl acetate:hexane=0:100 to 100:0, gradient). A solution of the obtained partially purified product (602 mg) and 4 M hydrochloric acid (1,4-dioxane solution, 0.69 mL) in methanol (2 mL) was stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (331 mg, quant.) as a colorless solid.

المصدر