4-Bromopyridinium chloride → 1-{(2S,4R)-1-benzyl-4-(t-butyl-dimethylsilyloxy)pyrrolidin-2-yl}-1-(4-pyridyl)methanol

HRID 975665Notes

Reaction equation

HRID 975665 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.C(=O)([O-])O.[Na+].C([Li])CCC.[CH2:19]([N:26]1[CH2:30][C@H:29]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:28][C@H:27]1[CH:39]=[O:40])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(OCC)C.O>[CH2:19]([N:26]1[CH2:30][C@H:29]([O:31][Si:32]([C:35]([CH3:36])([CH3:37])[CH3:38])([CH3:34])[CH3:33])[CH2:28][C@H:27]1[CH:39]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)[OH:40])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 881004-Bromopyridinium chlorideHCID 516892Sodium BicarbonateHCID 50922891(2S,4R)-1-benzyl-2-formyl-4-(t-butyldimethylsilyloxy)pyrrolidineHCID 178418339Butyllithium

Product 1

HCID 570935711-{(2S,4R)-1-benzyl-4-(t-butyl-dimethylsilyloxy)pyrrolidin-2-yl}-1-(4-pyridyl)methanolYield 38.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 4-bromopyridine hydrochloride (18.57 g) in ethyl ether (50 ml) and water (50 ml) was neutralized with sodium hydrogen carbonate in water (50 ml). After stirring for 10 minutes, the mixture was extracted three times with ethyl ether. The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure to give a residue. To a solution of the residue in ethyl ether (300 ml) was added n-butyllithium (1.68N solution in n-hexane) (63 ml) under -60° C. After the addition, the mixture was stirred for 30 minutes at -78° C. Then (2S,4R)-1-benzyl-4-(t-butyldimethylsilyloxy)-2-formylpyrrolidine (30.52 g) was added dropwise to the mixture under -60° C. After the addition, the mixture was stirred at -70° C. for 30 minutes and then warmed to room temperature. The raction mixture was quenched with water and 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=3:7 to 1:1) to give 1-{(2S,4R)-1-benzyl-4-(t-butyl-dimethylsilyloxy)pyrrolidin-2-yl}-1-(4-pyridyl)methanol (14.68 g).

Workup

  1. extractionthe mixture was extracted three times with ethyl ether
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customto give a residue
  6. additionAfter the addition
  7. stirringthe mixture was stirred for 30 minutes at -78° C
  8. additionAfter the addition
  9. stirringthe mixture was stirred at -70° C. for 30 minutes
  10. customThe raction mixture was quenched with water
  11. extractionextracted three times with ethyl acetate
  12. washThe combined organic layer was washed with brine
  13. dry with materialdried over magnesium sulfate
  14. customevaporated under reduced pressure
  15. customchromatographed on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-f34cd37a8e2e4c648a1ce8846e964ead
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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