Tetrahydrofuran → HCID 86620019, compound

HRID 2355772Notes

Reaction equation

HRID 2355772 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH2:11][CH2:10][CH:9]=2)=[CH:4][N:3]=1.C1C[O:16]CC1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][N:3]=1.[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2([OH:16])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 59265941HCID 59265941, compound

Product 2

HCID 59265957HCID 59265957, compoundYield 26%HCID 86620019HCID 86620019, compoundYield 29%

Procedure

2-Chloro-5-(cyclopent-1-enyl)pyridine (1.5 g, 8.5 mmol) was dissolved in THF (30 mL) in an oven-dried, nitrogen-flushed 250 mL round bottom flask and the resulting solution cooled in a dry ice/acetone bath under nitrogen. BH3.THF complex (2.4 g, 28.0 mmol, 28 mL of a 1 M solution in THF) was added dropwise with stirring via syringe and the mixture was allowed to warm slowly to room temperature and stir overnight. 2 N NaOH (15 mL), ethanol (15 mL) and 35% H2O2 (10 mL) were added and the mixture stirred for 0.5 h and then diluted with EtOAc and 1 N HCl. The layers were separated and the organic layer washed with brine and aqueous NaHSO3, dried over Na2SO4, filtered through celite, and concentrated. Purification by flash chromatography (hexanes:EtOAc/10:1→2:1) gave in order of elution by-products 2-chloro-5-cyclopentylpyridine (0.45 g, 29%) and 1-(6-chloropyridin-3-yl)cyclopentanol (0.44 g, 26%) followed by the desired product trans-2-(6-chloropyridin-3-yl)cyclopentanol (0.25 g, 15%) as a clear oil: LC/MS (ESI) m/z 197, 1H NMR (300 MHz, CDCl3) δ 8.26 (d, 1H, J=2.4 Hz), 7.55 (dd, 1H, J=8.4, 2.4 Hz), 7.25 (d, 1H, J=8.4 Hz), 4.12 (m, 1H), 2.88 (m, 1H), 2.24-1.62 (m, 6H).

Workup

  1. customflushed 250 mL round bottom flask
  2. temperaturethe resulting solution cooled in a dry ice/acetone bath under nitrogen
  3. additionBH3.THF complex (2.4 g, 28.0 mmol, 28 mL of a 1 M solution in THF) was added dropwise
  4. stirringstir overnight
  5. addition2 N NaOH (15 mL), ethanol (15 mL) and 35% H2O2 (10 mL) were added
  6. stirringthe mixture stirred for 0.5 h
  7. additiondiluted with EtOAc and 1 N HCl
  8. customThe layers were separated
  9. washthe organic layer washed with brine and aqueous NaHSO3
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered through celite
  12. concentrationconcentrated
  13. customPurification by flash chromatography (hexanes:EtOAc/10:1→2:1)

Sources & evidence

ORD record
ord-7f538619a1b0471d8f5ca1c988d5e53b
Source dataset
uspto-grants-2010_07
Patent number
US07754888B2

Reaction notes

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