Hydrochloric Acid → 1000210-63-8

Participants

Reaction Conditions

Reaction Steps

The 60 L reactor is charged with ethanol (24 L) and (2-{7-[4-(Tetrahydro-pyran-2-yloxy)-phenyl]-isoquinoline-5-sulfonyl}-ethyl)-carbamic acid tert-butyl ester (2.652 kg; 5.173 moles). The (2-{7-[4-(Tetrahydro-pyran-2-yloxy)-phenyl]-isoquinoline-5-sulfonyl}-ethyl)-carbamic acid tert-butyl ester is rinsed in with ethanol (2.6 L). Hydrochloric acid solution (31.9%; 1780 g; 15.6 moles) is diluted with water (1.42 L). This HCl solution is charged to the reactor and rinsed in with water (0.2 L). The reaction is warmed to 70° C. A yellow solution forms around 30° C. and a yellow slurry reforms near 70° C. The reaction is held at 70° C. for ½ hr and then is warmed up to reflux (78° C.). HPLC indicates a complete reaction after 1.5 hrs at reflux. Water (14.5 L) is added to the reaction over 13 minutes. The temperature drops to 69° C. The reaction is heated back to reflux (80° C.) and a solution forms. The reaction is cooled to 68° C. and solid begins forming. The reaction is held at 68° C. for ½ hr and then cools to 2° C. over 1.5 hrs. The slurry is held at 1-2° C. for 1 hr. The solid is filtered and washed with ethanol (4.6 L). The wet cake weight is 3.236 kg. The solid is dried in vacuo at 50° C. to give 2.106 kg (101.4% of theory) 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol di-hydrochloride salt. Mass Spectrum (LCMS) m/z=402.31) (M+H).

Provenance & Evidence