Formaldehyde → Methyl 9H-pyrido(3,4-b)indole-3-carboxylate

Beteiligte Stoffe

Reaktionsschritte

This compound was prepared by a modification of a known procedure (Couts et al., Heterocycles 1984, 22:131). To a mixture of the free base of L-tryptophan methyl ester (161 g, 0.738 mol) and paraformaldehyde (22 g, 0.733 mol) was added toluene (1 L). The mixture was refluxed with efficient mechanical stirring, and the water removed using a Barrett trap. After 1 hour, nearly the theoretical amount of water was collected (13 mL). Trifluoroacetic acid (5 mL, 0.065 mol, 8.8 mol %) was added through the top of the condenser (exothermic), and the mixture refluxed for another 1.5 hours. The solvent was evaporated and 10% palladium-on-carbon was added to the pot (44 g of moist material recovered from a previous run; dry wt=38 g based on water removed in subsequent step; ˜0.036 mol Pd, or 4.8 mol %). Xylene (800 mL) was added, and the mixture vigorously stirred (mechanical stirrer) and refluxed overnight with a Barrett trap to remove the water from the Pd/C. The reaction mixture was then cooled in an ice bath, then in a freezer at −20° C. overnight. The resulting sludge was filtered, affording mother liquors containing impurities, including a compound consistent with methyl 2-methyl-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylate, and a gray filter cake containing a mixture of the product and Pd/C. The filter cake was transferred to a paper thimble and extracted in a Soxhlet apparatus with methanol (800 mL in a 2-L recovery flask) in several batches. As the product crystallized in the pot, the slurry was filtered, the light yellow solid was washed with methanol and dried, and the filtrate was returned to the pot. Three batches of product were collected, affording a total of 76 g of product (46% yield from tryptophan methyl ester).

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