Reacción #1351644

Ecuación de reacción

water

3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propionic acid

2,3-difluoro-4-ethoxyphenol

dicyclohexylcarbodiimide

→

2,3-difluoro-4-ethoxyphenyl 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propionate

Rendimiento 102.5%

Disolventes

dichloromethane

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroIn a 3-L three-neck flask equipped with a stirrer
2. 2
   Otroto prepare a solution, which
3. 3
   workup.ADDITIONwas added dropwise to the reaction mixture at room temperature
4. 4
   workup.ADDITIONAfter dropwise adding
5. 5
   workup.STIRRINGthe solution was stirred at room temperature for 14 hours
6. 6
   Filtraciónwere filtered
7. 7
   Lavadothe filtrate was washed with 300 ml of 3M hydrochloric acid, 300 ml of water, 300 ml of a saturated aqueous sodium hydrogencarbonate solution and 600 ml of water
8. 8
   Secadodried over anhydrous magnesium sulfate
9. 9
   workup.DISTILLATIONThe solvent was distilled off from the reaction solution
10. 10
    Otroto obtain 56.4 g of a concentrated substance, which
11. 11
    Otrowas then purified by means of a silica gel column chromatography with a mixed solvent of heptane/ethyl acetate (7/3)

Procedimiento

In a 3-L three-neck flask equipped with a stirrer, a thermometer and a dropping funnel, 32.0 g (114.9 mmol) of 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propionic acid and 20.0 g (114.9 mmol) of 2,3-difluoro-4-ethoxyphenol were dissolved in 1000 ml of dichloromethane at room temperature under nitrogen atmosphere, and 15.4 g (126.4 mmol) of 4-dimethylaminopyridine was added thereto. The solution was stirred for 30 minutes thereafter, and then 26.1 g (126.4 mmol) of dicyclohexylcarbodiimide was dissolved in 400 ml of dichloromethane to prepare a solution, which was added dropwise to the reaction mixture at room temperature. After dropwise adding, the solution was stirred at room temperature for 14 hours. 500 ml of water was added to the reaction solution, insoluble materials were filtered, and then the filtrate was washed with 300 ml of 3M hydrochloric acid, 300 ml of water, 300 ml of a saturated aqueous sodium hydrogencarbonate solution and 600 ml of water and dried over anhydrous magnesium sulfate. The solvent was distilled off from the reaction solution under reduce pressure to obtain 56.4 g of a concentrated substance, which was then purified by means of a silica gel column chromatography with a mixed solvent of heptane/ethyl acetate (7/3) used as a developing solvent to obtain 51.4 g of 2,3-difluoro-4-ethoxyphenyl 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propionate as colorless crystals.

Fuente