Hydrochloric Acid → 1-(4-Chloro-3-methoxyphenyl)piperazine dihydrochloride

Temperature

60 °C

A 4-L beaker equipped with a mechanical stirrer was charged with tert-butyl 4-(4-chloro-3-methoxyphenyl)piperazine-1-carboxylate (500 g, 1.53 mol, 1 equiv) and MeOH (1.50 L). While stirring at room temperature conc. 37% HCl (500 mL, 4 equiv) was added over 5 min. The internal temperature rose to 40° C., and the solution became thick with precipitate. After 15 min, the mixture was heated to an internal temperature of 60° C. on a hotplate. (Foaming begun at approximately 50° C. as the mixture warms.) After 2 h at 60° C., the solution was cooled to room temperature, and subsequently to 5° C. in a refrigerator. The product was collected by filtration in two batches. Each batch of the red-brown filtrate was washed with EtOAc (2×500 mL) to give a light yellow solid. The two batches were combined to afford the product (391.3 g). The filtrate was concentrated to a volume of 300 mL in vacuo and treated with hot (50° C.) MeOH (500 mL). The mixture was cooled to 5° C. in a refrigerator for 24 h. The resulting precipitate was collected by filtration and washed with EtOAc (2×200 mL) to afford an additional 44.3 g of product (total of 435.6 g, 95% yield).

1. customA 4-L beaker equipped with a mechanical stirrer
2. additionwas added over 5 min
3. customrose to 40° C.
4. customFoaming begun at approximately 50° C. as the mixture
5. wait) After 2 h at 60° C.
6. temperaturethe solution was cooled to room temperature
7. customsubsequently to 5° C.
8. filtrationThe product was collected by filtration in two batches
9. washEach batch of the red-brown filtrate was washed with EtOAc (2×500 mL)
10. customto give a light yellow solid

ORD record

ord-5a1a033da9194e7883bf3006331a57bd

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296740B2