Triethylsilane → 3-(3,4-Difluorophenyl)pyrrolidin-3-ol

HRID 1931871Notes

Reaction equation

HRID 1931871 reaction equation
C([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)([OH:13])[CH2:9]1)C1C=CC=CC=1.C([SiH](CC)CC)C>[Pd].CO>[F:21][C:16]1[CH:15]=[C:14]([C:10]2([OH:13])[CH2:11][CH2:12][NH:8][CH2:9]2)[CH:19]=[CH:18][C:17]=1[F:20]

Participants

5

Reactant 2

HCID 12052Triethylsilane2×HCID 671736601-Benzyl-3-(3,4-difluorophenyl)pyrrolidin-3-ol

Product 1

HCID 635869723-(3,4-Difluorophenyl)pyrrolidin-3-olYield 93.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of enantiomer E1 of 1-benzyl-3-(3,4-difluorophenyl)pyrrolidin-3-ol (0.81 g, 2.8 mmol), methanol (15 mL) and palladium on carbon (160 mg) was purged with nitrogen. Triethyl silane (6.5 g, 56 mmol) was added drop wise and the resulting mixture was stirred at ambient temperature for 3 h after which the mixture was filtrated over celite and evaporated. Methanol (15 mL) and palladium on carbon (160 mg) was added and the mixture was purged with nitrogen. Triethyl silane (6.5 g, 56 mmol) was added in 5 equal portions over 1.5 h and the resulting mixture was stirred at ambient temperature for 11.5 h. The mixture was filtrated over celite, evaporated and purified on a Biotage (solute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1) to give the title compound (0.52 g). MS m/z (relative intensity, 70 eV) 199 (M+, bp), 141, (97), 127 (54), 114 (48), 113 (85).

Workup

  1. customwas purged with nitrogen
  2. filtrationwas filtrated over celite
  3. customevaporated
  4. additionMethanol (15 mL) and palladium on carbon (160 mg) was added
  5. customthe mixture was purged with nitrogen
  6. stirringthe resulting mixture was stirred at ambient temperature for 11.5 h
  7. filtrationThe mixture was filtrated over celite
  8. customevaporated
  9. custompurified on a Biotage (
  10. washsolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1)

Sources & evidence

ORD record
ord-8d3194c011f94fe6a28c4d0ff4f40bbc
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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