Hydrochloric Acid → HCID 13589642, compound

HRID 1589639Notes

Reaction equation

HRID 1589639 reaction equation
[C:1]1(=[O:7])O[C:4](=O)[CH2:3][CH2:2]1.[NH2:8][CH2:9][CH2:10][C:11]1[N:12]([CH3:16])[CH:13]=[CH:14][CH:15]=1.[BH4-].[Na+].Cl>C1COCC1.C(O)C>[CH3:16][N:12]1[C:11]2[CH2:10][CH2:9][N:8]3[CH:4]([C:15]=2[CH:14]=[CH:13]1)[CH2:3][CH2:2][C:1]3=[O:7]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 7922Succinic anhydrideHCID 5650581-methyl-1H-pyrrole-2-ethylamineHCID 4311764Sodium borohydride

Product 1

HCID 13589642HCID 13589642, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

A mixture of 110.9 g (1.098 mole) of succinic anhydride and 985 ml of THF was cooled to 10° C. and a solution of 140.53 g (1.098 mole) of 2-(2-aminoethyl)-1-methylpyrrole in 1400 ml of THF was added dropwise over a period of thirty minutes while stirring under an atmosphere of argon, the temperature being maintained at 10 to 15° C. After the addition was complete, stirring was continued an additional one hour and then the solvent removed in vacuo to give a dark-brown, oily residue. The residue was stirred and heated at 175° in an oil bath for three hours under an atmosphere of argon. The residue was distilled on a Kugelrohr apparatus, collecting the product imide at 170° C./0.06 mm, which crystallized to yield an off white solid, mp 116°-121° C. A small sample of the intermediate imide was recrystallized from ethanol to yield a white solid, mp 120°-122° C. A solution of 100 g (0.485 mole) of the above-obtained crude imide was added to 3-1 of 90% aqueous ethanol and the mixture cooled in an ice bath to about 3° C. Sodium borohydride (68.42 g; 1.81 moles) was added and about 25 ml of 2N hydrochloric acid was added dropwise with stirring over a five hour period by means of a metering pump while maintaining a temperature of 0° to 3° C. After the addition was complete (pH=8-9), the reaction was acidified with 1-1 of 2N hydrochloric acid over a period of 1.5 hours while maintaining a temperature of less than 10° C. Stirring (under nitrogen) was continued overnight as the temperature was allowed to gradually warm to ambient, during which time the mixture became a clear, colorless solution. The solvent was partially removed in vacuo using low heat to a final volume of about 800 mls, diluted with 800 mls of water and extracted three times with 300 ml portions of methylene chloride. The combined extracts were washed with 300 ml of water, 300 ml of brine, and dried over anhydrous potassium carbonate. The solvent was removed in vacuo to give 31.07 g of a crude tan solid. The crude solid was recrystallized from about 100 ml of hot EtOAc to give 23.76 g of nearly pure 4,5,7,8,9,9a-hexahydro-3-methyl-3H-pyrrolo[2,3-g]indolizin-7-one, an off-white solid, mp 122°-125° C.

Workup

  1. temperaturethe temperature being maintained at 10 to 15° C
  2. additionAfter the addition
  3. stirringstirring
  4. customthe solvent removed in vacuo
  5. customto give a dark-brown, oily residue
  6. stirringThe residue was stirred
  7. temperatureheated at 175° in an oil bath for three hours under an atmosphere of argon
  8. distillationThe residue was distilled on a Kugelrohr apparatus
  9. customcollecting the product imide at 170° C./0.06 mm, which
  10. customcrystallized
  11. customto yield an off white solid, mp 116°-121° C
  12. customA small sample of the intermediate imide was recrystallized from ethanol
  13. customto yield a white solid, mp 120°-122° C
  14. customA solution of 100 g (0.485 mole) of the above-obtained crude imide
  15. temperaturethe mixture cooled in an ice bath to about 3° C
  16. stirringwith stirring over a five hour period by means of a metering pump
  17. temperaturewhile maintaining a temperature of 0° to 3° C
  18. additionAfter the addition
  19. temperaturewhile maintaining a temperature of less than 10° C
  20. stirringStirring (under nitrogen)
  21. waitwas continued overnight as the temperature
  22. temperatureto gradually warm to ambient, during which time the mixture
  23. customThe solvent was partially removed in vacuo
  24. temperatureusing low heat to a final volume of about 800 mls
  25. additiondiluted with 800 mls of water
  26. extractionextracted three times with 300 ml portions of methylene chloride
  27. washThe combined extracts were washed with 300 ml of water, 300 ml of brine
  28. dry with materialdried over anhydrous potassium carbonate
  29. customThe solvent was removed in vacuo
  30. customto give 31.07 g of a crude tan solid
  31. customThe crude solid was recrystallized from about 100 ml of hot EtOAc

Sources & evidence

ORD record
ord-7c538e532e164bfca8e68a5cba5d82e0
Source dataset
uspto-grants-1986_02
Patent number
US04572911

Reaction notes

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