Ammonia → HCID 3045870, compound

HRID 1580149Notes

Reaction equation

HRID 1580149 reaction equation
[CH:1]1([C:5](Cl)=O)[CH2:4][CH2:3][CH2:2]1.[OH:8][C:9]1[CH:10]=[C:11]([C:15]23[CH2:22][CH:19]([NH:20][CH2:21]2)[CH2:18][CH2:17][CH2:16]3)[CH:12]=[CH:13][CH:14]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.N>O1CCCC1.O.CN(C)C=O.C(N(CC)CC)C>[OH:8][C:9]1[CH:10]=[C:11]([C:15]23[CH2:22][CH:19]([N:20]([CH2:5][CH:1]4[CH2:2][CH2:3][CH2:4]4)[CH2:21]2)[CH2:18][CH2:17][CH2:16]3)[CH:12]=[CH:13][CH:14]=1

Participants

10

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 78705Cyclobutanecarbonyl chlorideHCID 3045778HCID 3045778, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 3045870HCID 3045870, compoundYield 73.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

0.52 g of cyclobutylcarbonyl chloride is added to a mixture of 0.43 g of 1-(3-hydroxyphenyl)-6-azabicyclo[3,2,1]octane, 0.51 g of triethylamine and 8 ml of dimethylformamide. The mixture is stirred at room temperature for 15 hours. Then, water is added to the mixture, and the aqueous mixture is extracted with chloroform. The chloroform extract is washed with water, dried and then evaporated to remove solvent. The residue thus obtained is dissolved in 25 ml of tetrahydrofuran. 0.6 g of lithium aluminium hydride is added to the solution, and the solution is refluxed for 3 hours under heating. After cooling, water is added to the reaction solution to decompose lithium aluminium hydride. The reaction solution is acidified with hydrochloric acid. Then, the reaction solution is made alkaline with aqueous ammonia and extracted with chloroform. The chloroform extract is washed with water, dried and then evaporated to remove solvent. The residue is dissolved in 5 ml of chloroform. The chloroform solution is poured onto the column of 30 g of silica gel. Then, the column is eluted with a mixture of 500 ml of chloroform and 25 ml of methanol, and the effluent is evaporated to remove solvent. The residue thus obtained is distilled under reduced pressure, whereby 0.42 g of 1-(3-hydroxyphenyl)-6-cyclobutylmethyl-6-azabicyclo[3,2,1]octane is obtained as an viscous oil boiling at 240°C(bath temperature)/0.1 mmHg.

Workup

  1. extractionthe aqueous mixture is extracted with chloroform
  2. extractionThe chloroform extract
  3. washis washed with water
  4. customdried
  5. customevaporated
  6. customto remove solvent
  7. customThe residue thus obtained
  8. temperaturethe solution is refluxed for 3 hours
  9. temperatureunder heating
  10. temperatureAfter cooling
  11. extractionextracted with chloroform
  12. extractionThe chloroform extract
  13. washis washed with water
  14. customdried
  15. customevaporated
  16. customto remove solvent
  17. dissolutionThe residue is dissolved in 5 ml of chloroform
  18. additionThe chloroform solution is poured onto the column of 30 g of silica gel
  19. washThen, the column is eluted with a mixture of 500 ml of chloroform and 25 ml of methanol
  20. customthe effluent is evaporated
  21. customto remove solvent
  22. customThe residue thus obtained
  23. distillationis distilled under reduced pressure

Sources & evidence

ORD record
ord-ebd50de658fc454fb300d60f75d3bf12
Source dataset
uspto-grants-1976_01
Patent number
US03932429

Reaction notes

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