Hydrochloric Acid → Naratriptan Hydrochloride

Participants

Reaction Steps

A mixture of (E)-N-methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide (10 kg) and 10% palladium oxide on charcoal (10 kg, 50% wet paste, added as two charges) in DMF (50 L), water (20 L) and 2N hydrochloric acid (15 L) was hydrogenated at atmospheric pressure over 18.5 hr. The catalyst was removed by filtration. The filter cake was washed with water (20 L). The filtrate was concentrated in vacuo to approximately 30 L and cooled to 20°. Ethyl acetate (70 L) was added over 1 hr and the resulting suspension cooled to 5° and aged for 30 min. The product was collected by filtration, washed with ethyl acetate (20 L) and dried in vacuo at 40°-50° overnight (9.34 kg, 81.6% of theory). A portion (2.0 kg) of the solid was recrystallised from hot water (6.0 L) and obtained as white crystals (1.40 kg, 70% of theory).

Provenance & Evidence