Hydrochloric Acid → 7,9-Dimethyl-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one--hydrogen chloride (1/1)

Participants

Reaction Conditions

Reaction Steps

Charge a 5 L flask equipped, with an overhead stirrer, heating mantle, thermocouple, nitrogen purge and a teflon transfer line, with the mixture of tert-butyl 4-ethyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1,4-dicarboxylate and tert-butyl 4-methyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1,4-dicarboxylate (1286 g, 3.56 moles) dissolved in IPA (2 L) and heat the resulting mixture to 50° C. In a separate 12 L flask, equipped with an overhead stirrer, heating mantle, thermocouple, and nitrogen purge to a scrubber, add 5 N NaOH (1 L) and H2O (3 L). Thereafter add HCl (conc, 1.87 L, 21.8 moles) to the 12 L flask and heat to 50° C. Transfer the contents of the 5 L flask to the 12 L flask via the transfer line while flushing with N2 to remove the off gases from the reaction. After the addition, warm the resulting mixture to 80° C., and continue the N2 flush. After the reaction is complete allow the reaction mixture to cool to less than about 20° C. Add MTBE (4 L), and adjust the pH to neutral with aqueous NaOH. Transfer the resulting reaction mixture to a 22 L flask and separate the layers. Wash the aqueous layer with MTBE (2×2 L). Combine the organic washings and wash with brine (2 L), dry over MgSO4, filter and rinse with MTBE. Concentrate the filtrate to a dark oil. Dissolve in IPA (8 volumes) and transfer to a 12 L flask equipped with an overhead stirrer, thermocouple, 1 L addition funnel and N2 purge. Charge the addition funnel with HCl (conc. 765 mL) and add drop-wise over about 1 hr to the IPA solution. Stir the resulting slurry for about 1-2 hrs, filter, rinse the solids with cold IPA (3×500 mL), and dry the solid over night at about 50° C. to yield 561 g of the title compound.

Provenance & Evidence