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 (8.6 kg) and 10% palladium oxide on charcoal (2.58 kg, 50% wet pastel in DMF (86 L) and 2 N hydrochloric acid (12.3 kg) was hydrogenated at atmospheric pressure over 21 h. The catalyst was removed by filtration. The filter cake was washed with DMF/water (1:1; 30 L). The combined washings and filtrate were then treated with decolourising charcoal (0.86 kg) at 75°-80° for 2 h. The suspension was filtered and the residue washed with DMF/water (2×30 L). The filtrates from two hydrogenations could be combined for work-up. Thus the combined solutions were treated with 2M hydrochloric acid (1.72 L) then concentrated in vacuo to approximately 52 L. Ethyl acetate (120 L) was added, the resulting suspension cooled to 3° and aged for 1 h. The product was collected by filtration, washed with ethyl acetate (2×26 L) and dried in vacuo at 40°-50° overnight (15.96 kg, 83% of theory). Recrystallisation from hot IMS/water (7:1; 206 L) gave fine, off-white crystals (13.02 kg, 84% of theory).

Provenance & Evidence