Potassium Carbonate → 3-Methoxynaltrexone

Participants

Reaction Steps

To a suspension of Compound 3 (9.5 g, 31.5 mmol) in 80 mL of CH3CN was added K2CO3 (10.9 g, 79.0 mmol) portionwise followed by cyclopropylmethyl bromide (3.97 mL, 41.0 mmol) dropwise via syringe. The suspension was heated at reflux for 18 h. LC-MS showed a single peak corresponding to the desired product (Tr=0.830 min, M+H=356). The mixture was cooled to ambient temperature and the solid was filtered off and washed with CH3CN. The filtrate was concentrated and the golden yellow residue was diluted with CH2Cl2 and H2O. The layers were separated and the aqueous was further extracted with CH2Cl2. The combined organics were washed with brine, dried over MgSO4, filtered, and concentrated to provide 9.76 g (87%) of Compound 4 as a white foam that turned to a light yellow oily foam overnight. LC/MS, m/z=356.2 [M+H]+ (Calc: 356.43).

Provenance & Evidence