Benzyl Bromide → 6-[p-(Benzyloxy)phenyl]-3,4-dihydro-1-methylpyrrolo[1,2-a]pyrazine fumarate

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Reaction Steps

3,4-Dihydro-6-(4-hydroxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine (5.0 g), 100 ml of methylene chloride, 5.3 ml of benzyl bromide and 0.8 g of benzyltributylammonium bromide was added in succession to a solution of 1.8 g of sodium hydroxide in 100 ml of water under argon. The mixture was boiled under reflux overnight and stirred and subsequently cooled. After the addition of 100 ml of methylene chloride and 100 ml of water the phases were separated and the aqueous phase was extracted twice with 100 ml of methylene chloride each time. The organic phases were combined, dried with MgSO4 and freed from solvent. The residue, 10.3 g of brown oil, was chromatographed on 500 g of silica gel with methylene chloride/methanol mixtures (99:1 to 9:1) as the eluent. The crude product, 4.9 g of brown, amorphous material, was dissolved in a 10-fold amount of hot ethanol and treated with 1.1 equivalents of a saturated solution of fumaric acid in ethanol. The product, 2.2 g of yellow crystals, was recrystallized from a 20-fold amount of ethanol. There were obtained 1.8 g (19%) of 6-[p-(benzyloxy)phenyl]-3,4-dihydro-1-methylpyrrolo[1,2-a]pyrazine fumarate (1:1); m.pt.: 165°-168° C. (dec.).

Provenance & Evidence