Tetrahydrofuran → 3-(2-Methyl-pyridin-3-yl)-pentan-3-ol

HRID 1592422Notes

Reaction equation

HRID 1592422 reaction equation
CCO[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[N:8][C:7]=1[CH3:12])=[O:5].[CH3:13][CH2:14][Mg+].[Br-].[CH2:17]1COC[CH2:18]1>>[CH3:12][C:7]1[C:6]([C:4]([OH:5])([CH2:13][CH3:14])[CH2:17][CH3:18])=[CH:11][CH:10]=[CH:9][N:8]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 74401Ethyl 2-methylnicotinateHCID 178461630HCID 178461630, compound

Product 1

HCID 672728223-(2-Methyl-pyridin-3-yl)-pentan-3-olYield 40%

Procedure

To a stirred solution of ethyl 2-methyl nicotinate (1.04 g, 6.30 mmol) in dry THF (30 mL) was slowly added EtMgBr (3.0 M in Et2O, 5.2 mL, 16 mmol). The mixture was warmed to reflux and stirred for 60 h under N2. The suspension was cooled, poured into ice (50 mL) and stirred for 3 h. The layers were separated, and the aqueous layer was extracted with Et2O (5×100 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (1:1 Et2O/CH2Cl2), affording 3-(2-methyl-pyridin-3-yl)-pentan-3-ol as a yellow solid (0.447 g, 40%). 1H NMR (CDCl3) δ 0.77 (t, 6H, J=7.5 Hz), 1.80-2.12 (m, 4H), 2.70 (s, 3H), 7.12 (dd, 1H, J=4.8, 7.8 Hz), 7.87 (dd, 1H, J=7.8, 1.5 Hz), 8.39 (dd, 1H, J=4.8, 1.5 Hz).

Workup

  1. temperatureThe mixture was warmed
  2. temperatureto reflux
  3. temperatureThe suspension was cooled
  4. stirringstirred for 3 h
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with Et2O (5×100 mL)
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationAfter filtration the solvent
  9. customwas removed by evaporation under vacuum
  10. customthe residue was purified by flash chromatography on a silica gel column (1:1 Et2O/CH2Cl2)

Sources & evidence

ORD record
ord-fdb9d25821f04020b4a9fcdafb3cb083
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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