反应详情

Sodium hydride (1.86 g, 78 mmol) was dispersed in 30 ml DMF and added with (S)-2-hexanol (6.81 g, 66.6 mmol) with stirring while cooling with ice. After cooling with ice for another one hour, the mixture was stirred at room temperature for 9 hours and cooled again with ice, followed by adding gradually 4-fluorobenzonitrile (8.88 g, 73.3 mmol). After the reaction was continued at room temperature overnight, the mixture was added with 1 ml water while cooling with ice to inactivate excess sodium hydride, followed by removal of DMF in vacuum. The residue was added with 10 grams potassium hydroxide, 10 ml water and 50 ml ethylene glycol and cooled down at room temperature after being heated at a temperature of 200° C. while being refluxed for 9 hours. A crystalline product was dispersed by adding 200 ml water and thereafter carboxylic acid was liberated by acidifying with 3N hydrochloric acid. The carboxylic acid thus obtained was subjected to extraction with ethyl acetate and then washed with use of a saturated solution of sodium chloride. A coarse crystalline product derived after removal of the solvent was recrystallized from acetnitrile thereby obtaining the intended product (16.1 g, 64.8 mmol, 97%).

1. temperaturewhile cooling with ice
2. temperatureAfter cooling with ice for another one hour
3. stirringthe mixture was stirred at room temperature for 9 hours
4. temperaturecooled again with ice
5. customfollowed by removal of DMF in vacuum
6. additionThe residue was added with 10 grams potassium hydroxide, 10 ml water and 50 ml ethylene glycol
7. temperatureafter being heated at a temperature of 200° C.
8. temperaturewhile being refluxed for 9 hours
9. additionA crystalline product was dispersed
10. additionby adding 200 ml water