反应详情

A mixture containing 50 g of p-fluoroacetophenone and 150 ml of 40% aqueous dimethylamine is warmed in a pressure bottle at 90°-100° C. After two hours, a pale yellow oil is formed. The mixture is cooled, and the oil solidifies. The solid is collected and washed well with H2O to give 54.93 of p-dimethylaminoacetophenone, mp 101°-103° C., after heptane recrystallization. A 72 g sample of this acetophenone is heated with 129 g of N-chlorosuccinimide in 700 ml of toluene to reflux temperature and maintained at this temperature for 35 minutes. The mixture is cooled and filtered. The filter cake is washed with 200 ml of toluene, and the filtrate and wash solution are evaporated to dryness in vacuo to afford 66 g of oil. This oil is chromatographed on SiO2 with 40% hexane/CH2Cl2 to give 38.9 g of 3.5-dichloro-4-dimethylaminoacetophenone as a yellow oil. A 5.22 g sample of this oil is added portionwise to 2.75 g of SeO2 in 20 ml of dioxane and 0.7 ml of H2O at 55°-60° C. This mixture is heated at reflux temperature for 4.5 hours, cooled and filtered through siliceous earth. The filter cake is washed with 20 ml of dioxane. The dioxane solutions are cooled to 15° C. and 2.77 g of t-butylamine is added dropwise to afford a tan precipitate. After stirring 15 minutes at room temperature, the mixture is diluted with 200 ml of ethanol, cooled to 5° C. and 7 g of NaBH4 is added portionwise. After 15 hours, the mixture is treated with 300-400 g of ice and 200 ml of H2O at below 10° C. The mixture is stirred to dissolve all solids and extracted with 300 ml of CH2Cl2. The CH2Cl2 layer is washed with 100 ml of H2O, dried (MgSO4) and evaporated to dryness in vacuo to give 5.6 g of orange oil. This oil is dissolved in ethyl ether, decolorized with activated carbon and concentrated to 15 ml. On cooling, crystals are obtained. The title product is collected as white crystals, mp 96°-99° C.

1. temperatureis warmed in a pressure bottle at 90°-100° C
2. customa pale yellow oil is formed
3. temperatureThe mixture is cooled
4. customThe solid is collected
5. washwashed well with H2O