Methyl chloroformate → HCID 13457899, compound

HRID 462727Notes

Reaction equation

HRID 462727 reaction equation
C[N:2]1[CH2:21][CH2:20][N:5]2[CH2:6][C@@H:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:8]3[C:13]([C@@H:4]2[CH2:3]1)=[CH:12][CH:11]=[CH:10][CH:9]=3.[Na].[Cl:23]C(OC)=O>C(Cl)(Cl)Cl>[ClH:23].[ClH:23].[C:14]1([C@H:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C@@H:4]3[CH2:3][NH:2][CH2:21][CH2:20][N:5]3[CH2:6]2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 5360545SodiumHCID 13457892HCID 13457892, compound

Product 1

HCID 13457899HCID 13457899, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred solution of cis-1,3,4,6,7,11b-hexahydro-2-methyl-7-phenyl-2H-pyrazino[2,1-a]isoquinoline (11.0 g, 0.039 m) in chloroform (1500 ml) was added sodium bicarbanate (83.1 g, 0.99 m) and methyl chloroformate (45.3 g, 0.48 m), and the mixture heated to reflux for 48 hours. The salts were removed by filtration and the organic phase washed with 5% HCl (3×300 ml) and water (300 ml) and dried over MgSO4. The solvent was evaporated and the oily residue treated with 95% hydrazine (250 ml) and refluxed for 24 hours. Water (500 ml) was added and the mixture evaporated to an oily residue. This was treated with water (500 ml) and a small amount of 50% NaOH to ensure pH 11, and the mixture extracted with chloroform (3×250 ml). The extracts were dried over MgSO4 and evaporated to a yellow oil. This was dissolved in methanol (50 ml) and isopropanol (50 ml) and acidified with HCl gas. Upon standing and cooling, a white solid crystallized, which was collected by filtration. Recrystallization from methanol/isopropanol/water and vacuum drying gave 6.4 g of cis-1,3,4,6,7,11b-hexahydro-7-phenyl-2H-pyrazino[2,1-a]isoquinoline dihydrochloride, m.p. 275°-277°. The product has an ad cyc H rating greater than 1×10-5M, a (3H)mepyramine rating greater than 1×10-6M and a (3H)QNB of 9.2×10-7M.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 48 hours
  3. customThe salts were removed by filtration
  4. washthe organic phase washed with 5% HCl (3×300 ml) and water (300 ml)
  5. dry with materialdried over MgSO4
  6. customThe solvent was evaporated
  7. additionthe oily residue treated with 95% hydrazine (250 ml)
  8. temperaturerefluxed for 24 hours
  9. additionWater (500 ml) was added
  10. customthe mixture evaporated to an oily residue
  11. additionThis was treated with water (500 ml)
  12. extractionthe mixture extracted with chloroform (3×250 ml)
  13. dry with materialThe extracts were dried over MgSO4
  14. customevaporated to a yellow oil
  15. dissolutionThis was dissolved in methanol (50 ml)
  16. temperaturecooling
  17. customa white solid crystallized
  18. filtrationwhich was collected by filtration
  19. customRecrystallization from methanol/isopropanol/water and vacuum
  20. customdrying

Sources & evidence

ORD record
ord-79960db37ee8460e9b2e7d1b608ec5d2
Source dataset
uspto-grants-1985_05
Patent number
US04517187

Reaction notes

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