反应详情

温度

102.5 °C

To a solution of 54.5 kg of (S)-(−)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile in 255 lit DMSO was added 66.0 kg of anhydrous K2CO3 and 36.7 kg of 2,5-dichloronitrobenzene at room temperature and stirred for 16 hours at 100-105° C. To the reaction mixture 2550 lit of water was added at about 30° C. The reaction mixture was extracted with toluene, the toluene layer was washed with water and 5% sodium hydroxide solution and after acid base treatment yielded an oily product. The oil was dissolved in 435 lit IPA at 30° C. and 17.7 kg of oxalic acid dihydrate was added to it, heated to 70-75° C., stirred and charcolized the clear solution, cooled, The filtrate was cooled to 5-10° C. slowly and the resultant solid was filtered, dried at 60° C. and micronised to get the oxalic acid salt of (S)-(+)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile.

1. extractionThe reaction mixture was extracted with toluene
2. washthe toluene layer was washed with water and 5% sodium hydroxide solution
3. customafter acid base treatment yielded an oily product
4. dissolutionThe oil was dissolved in 435
5. customat 30° C.
6. temperatureheated to 70-75° C.
7. stirringstirred
8. temperaturecooled
9. temperatureThe filtrate was cooled to 5-10° C. slowly
10. filtrationthe resultant solid was filtered
11. customdried at 60° C.