2,3-Dihydroxybutanedioic Acid → N-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-pyrrolidineacetic acid methyl ester

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Reaction Steps

A mixture of 2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethylchloride (1.5 g, 4.9 mmol, prepared as described in Example 15), methyl 3-pyrrolidineacetate acetate (2.0 g, 9.8 mmol), potassium carbonate (2.4 g, 17 mmol) and potassium iodide (0.16 g) in methylisobutyl ketone (30 ml) was heated at reflux temperature for 48 h. The reaction mixture was allowed to cool and water (40 ml) was added. The phases were separated and from the organic phase the solvent was evaporated in vacuo to give an oily residue. This residue was dissolved in a mixture of ethyl acetate (25 ml) and water (25 ml) and pH was adjusted to 4 with a 34% aqueous tartaric acid solution. The phases were separated and the organic phase was discarded. Ethyl acetate (25 ml) was added to the aqueous phase and pH was adjusted to approx. 9 with a 2 M aqueous sodium hydroxide solution. The phases were separated and from the organic phase the solvent was evaporated in vacuo to give an oily residue which was submitted to column chromatography on silica gel (180 ml) using a mixture of THF and n-heptane (1:1) as eluent. Collecting the proper fraction afforded 1.0 g of N-(2-(2 -(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-pyrrolidineacetic acid methyl ester as an oil.

Provenance & Evidence