Methane → 1000210-66-1

Participants

Reaction Conditions

Reaction Steps

Ethanol (8 L) and 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol di-hydrochloride salt (841.6 g; 2.097 moles) are charged to a 22 L flask equipped with overhead stirring, condenser, nitrogen inlet, heating mantle, thermocouple, and addition funnel. The 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol di-hydrochloride salt is rinsed in with ethanol (3.28 L). The reaction is warmed to 55° C. Sodium hydroxide solution (1100 mL; 1.91 N; 2.10 moles) is added to the reaction over 7 minutes during which time the temperature increases to 62° C. The reaction is heated to reflux (78° C.) and held for 1 hr. Water (1.96 L) is added to the reaction at once. The temperature decreases to 68° C. The reaction is heated back to reflux (79° C.) and a solution forms. Darco G-60® (438 g) is added to the reaction. The reaction is held at reflux for 1.25 hours. The hot Darco G-60® slurry is filtered through GFF paper into another 22 L flask. A light yellow solution results. The original flask and Darco G-60® filter cake are rinsed with hot ethanol (2.5 L). During the rinse, solid begins to form in the filtrate. The 22 L flask containing the filtrate and wash is equipped with overhead stirring, nitrogen inlet, and a thermocouple. The slurry is stirred and allowed to cool to ambient temperature. The solid is filtered and washed with ethanol (2 L). The wet cake weight is 672 g. The solid is dried in vacuo at 50° C. to give 540 g (68.9% yield) of 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol monohydrochloride hemihydrate. Mass Spectrum (LCMS) m/z=329.3) (M+H+).

Provenance & Evidence