Ammonia → 3-[7-Methyl-6-(2-phenylethyl)-6-azabicyclo[3.2.1]octan-1-yl]phenol--hydrogen chloride (1/1)

HRID 1580150Notes

Reaction equation

HRID 1580150 reaction equation
[C:1]1([CH2:7][C:8]([Cl:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:11][C:12]1[CH:13]=[C:14]([C:18]23[CH2:26][CH:22]([NH:23][CH:24]2[CH3:25])[CH2:21][CH2:20][CH2:19]3)[CH:15]=[CH:16][CH:17]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.N>O1CCCC1.C(Cl)Cl.C(N(CC)CC)C>[ClH:10].[OH:11][C:12]1[CH:13]=[C:14]([C:18]23[CH2:26][CH:22]([N:23]([CH2:8][CH2:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:24]2[CH3:25])[CH2:21][CH2:20][CH2:19]3)[CH:15]=[CH:16][CH:17]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 7679Phenylacetyl chlorideHCID 3045733HCID 3045733, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 681444093-[7-Methyl-6-(2-phenylethyl)-6-azabicyclo[3.2.1]octan-1-yl]phenol--hydrogen chloride (1/1)Yield 15.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

0.62 g of phenylacetyl chloride is added dropwise under ice-cooling to a mixture of 0.35 g of 1-(3-hydroxyphenyl)7-methyl-6-azabicyclo[3,2,1]octane, 1 ml of triethylamine and 7 ml of methylenedichloride. The mixture is stirred at room temperature for 20 hours. Then, the mixture is concentrated under reduced pressure. Water is added to the residue, and the aqueous mixture is extracted with benzene. The benzene extract is washed with diluted hydrochloric acid, water, aqueous sodium bicarbonate and water, successively. The benzene extract is dried and evaporated to remove solvent. The residue thus obtained is dissolved in 12 ml of tetrahydrofuran. 0.6 g of lithium aluminium hydride is added to the tetrahydrofuran solution, and said solution is refluxed for 1.5 hours. After cooling, diluted hydrochloric acid is added to the reaction solution to decompose lithium aluminium hydride. 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 a column of 20 g of silica gel. Then, the column is eluted with a mixture of 300 ml of chloroform and 50 ml of methanol, and the effluent is evaporated to remove solvent. Methanolic hydrogen chloride is added to the residue in ether, and the crystalline precipitate is collected by filtration. The precipitate is recrystallized from acetone. 0.09 g of 1-(3-hydroxyphenyl)-6-phenethyl- 7-methyl-6-azabicyclo[3,2,1]octane hydrochloride is obtained. M.p. 231°-233°C.

Workup

  1. concentrationThen, the mixture is concentrated under reduced pressure
  2. additionWater is added to the residue
  3. extractionthe aqueous mixture is extracted with benzene
  4. extractionThe benzene extract
  5. washis washed with diluted hydrochloric acid, water, aqueous sodium bicarbonate and water
  6. extractionThe benzene extract
  7. customis dried
  8. customevaporated
  9. customto remove solvent
  10. customThe residue thus obtained
  11. temperatureis refluxed for 1.5 hours
  12. temperatureAfter cooling
  13. extractionextracted with chloroform
  14. extractionThe chloroform extract
  15. washis washed with water
  16. customdried
  17. customevaporated
  18. customto remove solvent
  19. dissolutionThe residue is dissolved in 5 ml of chloroform
  20. additionThe chloroform solution is poured onto a column of 20 g of silica gel
  21. washThen, the column is eluted with a mixture of 300 ml of chloroform and 50 ml of methanol
  22. customthe effluent is evaporated
  23. customto remove solvent
  24. additionMethanolic hydrogen chloride is added to the residue in ether
  25. filtrationthe crystalline precipitate is collected by filtration
  26. customThe precipitate is recrystallized from acetone

Sources & evidence

ORD record
ord-fb6a9d92cae8479281878ed9ebe52f1a
Source dataset
uspto-grants-1976_01
Patent number
US03932429

Reaction notes

Loading…