1,5-Diazabicyclo(4.3.0)non-5-ene → HCID 10782414, compound

HRID 400222Notes

Reaction equation

HRID 400222 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:17][CH2:16][CH2:15][C@@:14]2([CH3:18])[C@H:10]1[CH2:11][CH2:12][C@@H:13]2[C@H:19]([CH3:22])[CH:20]=[O:21])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1CN2C(=NCCC2)C1.[BH4-].[Na+].CCCCCC.C(OC(=O)C)C>C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(O)(C)C>[C:4]([Si:1]([CH3:3])([CH3:2])[O:8][C@H:9]1[CH2:17][CH2:16][CH2:15][C@@:14]2([CH3:18])[C@H:10]1[CH2:11][CH2:12][C@@H:13]2[C@@H:19]([CH3:22])[CH2:20][OH:21])([CH3:6])([CH3:7])[CH3:5]

Participants

8

Reactant 4

HCID 763491,5-Diazabicyclo(4.3.0)non-5-eneHCID 4311764Sodium borohydrideHCID 10853465HCID 10853465, compoundHCID 21226206Ethyl acetate hexane

Product 1

HCID 10782414HCID 10782414, compoundYield 50.7%

Reagents, catalysts & solvents 3

HCID 311Citric AcidSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1740 mg of (S)-2-[(1R,3aR,4S,7aR)-4-(tert-butyl-dimethylsilanyloxy)-7a-methyl-octahydro-inden-1-yl]-propan-1-al was dissolved in anhydrous THF (35 ml). DBN (640 ml; 5,36 mmol) was added and the mixture was refluxed for four hours. The reaction mixture, after cooling, was poured in cold citric acid solution, extracted with ethyl-acetate, washed with brine and dried over Na2 SO4. Removal of the solvent afforded a crude colourless oil (approximately 1:1 mixture at C(20)). The crude mixture was then dissolved in isopropanol (40 ml), cooled to 0° C., and NaBH4 (232 mg; 6,13 mmol) was added. The cooling bath was removed and stirring was continued for half an hour at room temperature. The reaction mixture was poured in cold brine, extracted with ethyl-acetate, dried over Na2 SO4. Removal of the solvent afforded a colourless oil. HPLC chromatography (eluent: n-hexane/ethyl-acetate 85:15) allowed the separation of both diastereoisomers affording 887 mg (50,7%) of the desired (R)-2-[(1R,3aR,4S,7aR)-4-(tert-Butyl-dimethyl-silanyloxy)-7a-methyl-octahydro-inden-1-yl]-propan-1-ol as a colourless oil.

Workup

  1. temperaturethe mixture was refluxed for four hours
  2. temperatureThe reaction mixture, after cooling
  3. extractionextracted with ethyl-acetate
  4. washwashed with brine
  5. customdried over Na2 SO4
  6. customRemoval of the solvent
  7. customafforded a crude colourless oil (approximately 1:1 mixture at C(20))
  8. customThe cooling bath was removed
  9. waitwas continued for half an hour at room temperature
  10. additionThe reaction mixture was poured in cold brine
  11. extractionextracted with ethyl-acetate
  12. customdried over Na2 SO4
  13. customRemoval of the solvent
  14. customafforded a colourless oil
  15. customthe separation of both diastereoisomers

Sources & evidence

ORD record
ord-2af931c3e7e942e085ba98aed45cee95
Source dataset
uspto-grants-1998_10
Patent number
US05827883

Reaction notes

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