HCID 131722209, compound → HCID 54430937, compound

HRID 1275165Notes

Reaction equation

HRID 1275165 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@H:11]1[O:16][CH2:15][C:14](=O)[N:13]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:12]1)(C(C)(C)C)(C)C>O1CCCC1>[Cl:25][C:20]1[CH:19]=[C:18]([N:13]2[CH2:14][CH2:15][O:16][C@H:11]([CH2:10][CH2:9][OH:8])[CH2:12]2)[CH:23]=[CH:22][C:21]=1[Cl:24]

Participants

3

Reactant 1

HCID 131722209HCID 131722209, compound

Product 1

HCID 54430937HCID 54430937, compoundYield 91.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

580 mg (1.43 mmole) of 2-[(2 R)-(3,4-dichlorophenyl)-5-oxomorpholin-2-yl]ethanol t-butyldimethylsilyl ether [prepared as described in step (b) above] were dissolved in 6 ml of anhydrous tetrahydrofuran. The solution was then heated under reflux under a stream of nitrogen and 0.60 ml (6.0 mmole) of a 10 M borane-dimethyl sulfide complex was added dropwise. The mixture was then stirred for 2 hours. At the end of this time, the solvent was removed by distillation under reduced pressure, and 5 ml of 1 N aqueous hydrochloric acid were added. The mixture was then stirred at 100° C. for 1 hour. The reaction mixture was air-cooled, made basic by the addition of a 1 N aqueous solution of sodium hydroxide, diluted with a saturated aqueous solution of sodium chloride and then extracted with ethyl acetate. The organic extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography, using a gradient elution method, with mixtures of methylene chloride and methanol ranging from 9:1 to 17:3 by volume as the eluent, to obtain 360 mg of the title compound.

Workup

  1. temperatureThe solution was then heated
  2. temperatureunder reflux under a stream of nitrogen and 0.60 ml (6.0 mmole) of a 10 M borane-dimethyl sulfide complex
  3. additionwas added dropwise
  4. customAt the end of this time, the solvent was removed by distillation under reduced pressure, and 5 ml of 1 N aqueous hydrochloric acid
  5. additionwere added
  6. stirringThe mixture was then stirred at 100° C. for 1 hour
  7. temperatureThe reaction mixture was air-cooled
  8. additionmade basic by the addition of a 1 N aqueous solution of sodium hydroxide
  9. additiondiluted with a saturated aqueous solution of sodium chloride
  10. extractionextracted with ethyl acetate
  11. extractionThe organic extract
  12. washwas washed with a saturated aqueous solution of sodium chloride
  13. dry with materialdried over anhydrous sodium sulfate
  14. customThe solvent was then removed by distillation under reduced pressure
  15. customThe resulting residue was purified by silica gel column chromatography
  16. washa gradient elution method

Sources & evidence

ORD record
ord-994255128a6a43bda060736e048b73b5
Source dataset
uspto-grants-2000_12
Patent number
US06159967

Reaction notes

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