Methanol → Methylnaltrexone Bromide

Participants

Reaction Steps

The foam (4) (597 mg) was dispersed in water (6 ml)/methanol (2 ml). Some dark oil remained undissolved. The clear supernatant liquid was decanted and applied to the prepared anion exchange resin column. The residue was washed twice with methanol (0.2 ml)/water (3 ml). The supernatant liquors were applied to the column. The column was eluted with 4.2 L of sterile water and fractions of ˜20 ml were collected. The presence of N-Methylnaltrexone salt was detected by liquid chromatography/mass spectrometry (LC/MS). The majority of N-Methylnaltrexone was located in the initial 1.5 L of eluate of which the first 600 ml contained the most pure material by TLC (4:1 dichloromethane/methanol, normal phase silica). The first 600 ml of eluate was combined and concentrated on the rotary evaporator to give a whitish glass. The water bath was maintained at ˜35° C. Care was needed to control foaming of the eluate while evaporating.

Provenance & Evidence