Hydrogen Bromide → HCID 135736932, compound

Participants

Reaction Steps

3,4-Dihydro-6-(p-methoxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine (20.9 g) was boiled with 500 ml of 48% hydrobromic acid in an argon atmosphere while stirring for 11/2 hours. The hydrobromic acid was removed in a vacuum and the residue was dissolved in 900 ml of ethyl acetate with the addition of 100 ml of methanol. The solution was stirred for 15 minutes with a mixture of 500 ml of saturated sodium hydrogen carbonate solution and 100 ml of 2N sodium hydroxide solution. The aqueous phase was brought to a pH value of 8-9 with 2N hydrochloric acid and extracted four times with 500 ml of an ethyl acetate/methanol mixture (9:1) each time. The aqueous phase was neutralized (pH=7) with 2N hydrochloric acid and continuously extracted overnight with 1000 ml of ethyl acetate. The organic phases were filtered, combined and concentrated to 150 ml. Then, 150 ml of ethyl acetate were added, the suspension was boiled and stored in a refrigerator overnight. 16.3 g of crude product were filtered off. 1.6 g thereof were dissolved in a 50-fold amount of methanol and a 10-fold amount of methylene chloride and treated with 1.1 equivalents of fumaric acid in 20 ml of methanol. There were obtained 1.8 g (62%) of 3,4-dihydro-6-(4-hydroxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine fumarate (1:1 ); m.pt.: 209°-213° C. (dec.).

Provenance & Evidence