Methylnaltrexone Synthesis

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Methylnaltrexone Synthesis
Type Total Synthesis
Chemical Name Methylnaltrexone
Systematic Name (5α)-17-(cyclopropylmethyl)-3,14-dihydroxy-17-methyl-4,5-epoxymorphinanium-17-ium-6-one
Reagents naltrexone, iodomethane
Chemicals
Equipment
Reactions
Yield 70.5%
Precautions
Primary Source [1]


An excess of concentrated ammonia was added to a concentrated aqueous solution of 18.2 gm (0.05 mol) of N-allyl-noroxymorphone hydrochloride, whereupon the free base precipitated, which was separated by extraction with chloroform. The combined chloroform extracts were dried with sodium sulfate and evaporated in vacuo. The residue was dissolved in 150 ml of absolute acetone, the resulting solution was admixed with 18 ml (0.29 mol) of methyl iodide in a pressure vessel, the vessel was sealed, and the reaction mixture contained therein was heated at 70° C. for three days. Thereafter, the reaction product which had separated out in crystalline form was collected by suction filtration, washed first with absolute acetone and then with absolute ether, and dried at 80° C. 16.6 gm (70.5% of theory) of N-Allyl-noroxymorphone methoiodide, having a melting point of 217°-218°C. were obtained. Additional crystalline reaction product was obtained by evaporation of the mother liquor.

Facts about Methylnaltrexone SynthesisRDF feed
Chemical Name Methylnaltrexone  +
Reagents Naltrexone, iodomethane  +
Synthesis Type Total Synthesis  +
Systematic Chemical Name (5α)-17-(cyclopropylmethyl)-3,14-dihydroxy-17-methyl-4,5-epoxymorphinanium-17-ium-6-one  +
Yield 70.5%  +