4,5,6,7-Tetrahydrothieno[3,2,c] pyridine hydrochloride

Chemical Properties

Off-White Solid

Uses

An intemediate of Clopidogrel and Prasugrel.

Synthesis

Example 5: Preparation of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride In a 2-liter four-necked flask equipped with a thermometer and a mechanical stirrer, 2-thiophene ethylamine (100 g, 0.79 mol) was added. The reaction was dissolved in dichloromethane (600 ml) at 25°C (±5°C) and stirred for 5 to 10 minutes. Subsequently, paraformaldehyde (26.4 g, 0.88 mole) was added to the reaction system and the reaction was subjected to azeotropic reflux at 40 to 45°C for 4 to 6 hours. Upon completion of the reaction, the system was cooled to room temperature and a N,N-dimethylformamide solution (200 ml) of 7% hydrochloric acid was slowly added at 25 °C (±5 °C). The reaction mixture was continued to be stirred at 70°C (±5°C) for 4 to 6 hours. Afterwards, the reaction solution was cooled to 15 °C (±2 °C) and stirred for 8 to 10 hours to promote crystallization. The solid product was collected by filtration and washed with pre-cooled dichloromethane. Finally, the product was dried under vacuum at 30 to 40 °C to afford 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride (120 g, 99% yield).

References

[1] Patent: WO2012/1486, 2012, A1. Location in patent: Page/Page column 18
[2] Journal of Organic Chemistry, 2015, vol. 80, # 14, p. 7019 - 7032
[3] Patent: EP1772455, 2007, A2. Location in patent: Page/Page column 9
[4] Journal of Organometallic Chemistry, 2009, vol. 694, # 13, p. 2092 - 2095
[5] Patent: US2004/24011, 2004, A1. Location in patent: Page 7