Hydrogen Bromide → HCID 135736932, compound

HRID 486570Notes

Reaction equation

HRID 486570 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]3[CH2:14][CH2:15][N:16]=[C:17]([CH3:18])[C:12]3=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.Br.C(Cl)Cl.[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27]>CO>[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27].[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:13]3[CH2:14][CH2:15][N:16]=[C:17]([CH3:18])[C:12]3=[CH:11][CH:10]=2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 6344DichloromethaneHCID 444972Fumaric AcidHCID 19095368HCID 19095368, compound

Product 1

HCID 135736932HCID 135736932, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.).

Workup

  1. customThe hydrobromic acid was removed in a vacuum
  2. dissolutionthe residue was dissolved in 900 ml of ethyl acetate with the addition of 100 ml of methanol
  3. stirringThe 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
  4. extractionextracted four times with 500 ml of an ethyl acetate/methanol mixture (9:1) each time
  5. customwith 2N hydrochloric acid and continuously extracted overnight
  6. filtrationThe organic phases were filtered
  7. concentrationconcentrated to 150 ml
  8. additionThen, 150 ml of ethyl acetate were added
  9. customstored in a refrigerator overnight
  10. filtration16.3 g of crude product were filtered off
  11. dissolution1.6 g thereof were dissolved in a 50-fold amount of methanol

Sources & evidence

ORD record
ord-7a6ed76dedc9409493f38729ea397189
Source dataset
uspto-grants-1994_03
Patent number
US05292732

Reaction notes

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