Acetic Acid → 1-{(2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethylsilyloxy) pyrrolidin-2-yl}-1-(4-pyridyl)methanol

HRID 975666Notes

Reaction equation

HRID 975666 reaction equation
C([N:8]1[CH2:12][C@H:11]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][C@H:9]1[CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[OH:22])C1C=CC=CC=1.C(O)(=O)C.O1CCCC1.Cl[C:39]([O:41][CH2:42][CH:43]=[CH2:44])=[O:40]>C(O)C.O.[OH-].[OH-].[Pd+2]>[CH2:42]([O:41][C:39]([N:8]1[CH2:12][C@H:11]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][C@H:9]1[CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[OH:22])=[O:40])[CH:43]=[CH2:44]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 18052Allyl chloroformateHCID 570935711-{(2S,4R)-1-benzyl-4-(t-butyl-dimethylsilyloxy)pyrrolidin-2-yl}-1-(4-pyridyl)methanol

Product 1

HCID 573185081-{(2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethylsilyloxy) pyrrolidin-2-yl}-1-(4-pyridyl)methanol

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 1-{(2S,4R)-1-benzyl-4-(t-butyldimethylsilyloxy) pyrrolidin-2-yl}-1-(4-pyridyl)methanol (32.73 g) in ethanol (300 ml) was added acetic acid (9.4 ml) and palladium hydroxide on carbon (10 g). The mixture was stirred vigorously under an atmosphere of hydrogen at room temperature for 6 hours. The palladium catalyst was removed by filtration and washed with ethanol. The combined organic layer was evaporated under reduced pressure to give a residue. To a solution of the residue in water (300 ml) and tetrahydrofuran (THF) (300 ml) was added dropwise allyl chloroformate (9.6 ml) under pH 9~10 at 0° C. After stirring the mixture at 0° C. for 1 hour, the reaction mixture was extracted three times with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was column chromatographed on silica gel (eluting with ethyl acetate:n-hexane=7:3) to give 1-{(2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethylsilyloxy) pyrrolidin-2-yl}-1-(4-pyridyl)methanol (21.74 g).

Workup

  1. customThe palladium catalyst was removed by filtration
  2. washwashed with ethanol
  3. customThe combined organic layer was evaporated under reduced pressure
  4. customto give a residue
  5. stirringAfter stirring the mixture at 0° C. for 1 hour
  6. extractionthe reaction mixture was extracted three times with ethyl acetate
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated under reduced pressure
  10. customchromatographed on silica gel (eluting with ethyl acetate:n-hexane=7:3)

Sources & evidence

ORD record
ord-c8925dd9cce440659d4487007a276b12
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

Loading…