Potassium Carbonate → N-{[(3S)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-yl]Methyl}-N-{[(2S)-8-methyl-2,3-dihydro[1,4]Dioxino[2,3-f]Quinolin-2-yl]methyl}amine

Participants

Reaction Conditions

Reaction Steps

Ethanol (grade 2B, 8.0 L) was charged to a charged to a (22-L) reactor equipped with an overhead stirrer, temperature controller, thermocouple, and reflux condenser. N-{[(3S)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-yl]methyl}-N-{[(2S)-8-methyl-2,3-dihydro[1,4]Dioxino[2,3-f]quinolin-2-yl]methyl}amine maleic acid salt, (800 g, 1.46 mole) (Example 93), was added to the reactor followed by solid potassium carbonate (325 mesh, 222 g, 1.6 mole). The slurry was heated with stirring under nitrogen at 49 to 52° C. for 1 h. The reaction mixture was allowed to cool to 20 to 24° C., stirred for 2 h and the solids were filtered through a funnel lined with polypropylene. The filter cake was washed with ethanol (grade 2B, 8.0 L). The combined ethanol filtrate and washes were concentrated to a volume of 2.8 to 3.0 L at 40 to 45° C. and 45-60 mm Hg. The concentrate was stirred for 20 h at 20-25° C. when solids separate out. Water (1 L) was added to the slurry and stirred for another 4 h at 20-25° C. followed by stirring for an additional 3 h at 10 to 15° C. The solids are filtered and the cake washed with a mixture of ethanol (grade 2B, 0.1 L) and water (0.7 L). The solid was dried under vacuum (<20 mm Hg) at 40° C. to give 469 g of N-{[(3S)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-yl]Methyl}-N-{[(2S)-8-methyl-2,3-dihydro[1,4]Dioxino[2,3-f]Quinolin-2-yl]methyl}amine (74% yield). Purity by HPLC is 98.5% (diastereomer content 1.1%), MW 431 (LC/MS).

Provenance & Evidence