Tetrahydrofuran → 1-(4-Fluorophenyl)-2-(4-pyridyl)ethanediol

HRID 1387619Notes

Reaction equation

HRID 1387619 reaction equation
C([Si](C)(C)O[CH2:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)(C)(C)C.C([N-]C(C)C)(C)C.[Li+].[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH:29]=[O:30])=[CH:27][CH:26]=1.C1C[O:36]CC1>>[F:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]([OH:36])([OH:30])[CH2:7][C:8]2[CH:9]=[CH:10][N:11]=[CH:12][CH:13]=2)=[CH:27][CH:26]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 680234-FluorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 109878804-(Tert-butyldimethylsilyloxymethyl)pyridine

Product 1

HCID 187715021-(4-Fluorophenyl)-2-(4-pyridyl)ethanediolYield 62%

Procedure

To a stirring solution of 2.0 g (11.2 mmol) 4-(t-butyldimethyl-silyloxy)methyl pyridine in 8 ml of THF at −20° C. was added 14.7 mmol of lithium di-iso-propyl amide in THF. Thirty minutes later 4-fluoro-benzaldehyde (1.66 g, 13.4 mmol) was added at which point the solution was allowed to warm slowly to rt. The reaction was quenched with NH4Cl and extracted with ether to afford the crude protected diol which following concentration was dissolved in THF and treated with 17 ml of a 1 molar solution of tetrabutylammonium fluoride in THF overnight. Standard aqueous workup afforded the crude diol which was further purified by column chromatography (hex/EtOAc) to yield 1.6 g (62%) of the titled material.

Workup

  1. customThe reaction was quenched with NH4Cl
  2. extractionextracted with ether
  3. customto afford the crude protected diol which
  4. concentrationconcentration
  5. dissolutionwas dissolved in THF
  6. additiontreated with 17 ml of a 1 molar solution of tetrabutylammonium fluoride in THF overnight
  7. customStandard aqueous workup afforded the crude diol which
  8. customwas further purified by column chromatography (hex/EtOAc)

Sources & evidence

ORD record
ord-42d9231aec49497e8f115279c497775e
Source dataset
uspto-grants-2001_07
Patent number
US06268370B1

Reaction notes

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