Hydrochloric Acid → 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetic acid

Temperature

40 °C

50.0 g of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride and 74.6 g of α-bromo-(2-chlorophenyl)acetic acid were successively added to a mixture of 275 ml of water and 75 ml of methanol, and the resulting solution was cooled to below 10° C. while stirring. 63.9 g of 85.0% KOH dissolved in 142 ml of water was slowly added to the above solution while maintaining the temperature at below 15° C. The resulting transparent solution was heated to 40° C. and stirred at that temperature for 3 hrs. The pH of the reaction solution was adjusted to 3.5 with 6N-HCl, cooled to room temperature and stirred for 2 hrs. Then, the reaction mixture was further cooled to below 5° C. and stirred for 2 hrs. The precipitated crystals were filtered, washed sequentially with 150 ml of water and 100 ml of n-hexane, and dried at 40° C. to obtain 81.7 g of the title compound (yield: 88%) as a white-yellow monohydrate.

1. temperaturethe resulting solution was cooled to below 10° C.
2. additionwas slowly added to the above solution
3. temperaturewhile maintaining the temperature at below 15° C
4. stirringstirred at that temperature for 3 hrs
5. temperaturecooled to room temperature
6. stirringstirred for 2 hrs
7. temperatureThen, the reaction mixture was further cooled to below 5° C.
8. stirringstirred for 2 hrs
9. filtrationThe precipitated crystals were filtered
10. washwashed sequentially with 150 ml of water and 100 ml of n-hexane
11. customdried at 40° C.

ORD record

ord-d297e685ed4d468f835a791f1885ccb0

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07763730B2