Methyl 2-(piperidin-1-yl)pyridine-4-carboxylate → [2-(Piperidin-1-yl)pyridin-4-yl]methanol

HRID 1174510Notes

Reaction equation

HRID 1174510 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]1([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][N:22]=2)[C:16](OC)=[O:17])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1>C1COCC1>[N:7]1([C:13]2[CH:14]=[C:15]([CH2:16][OH:17])[CH:20]=[CH:21][N:22]=2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1

Participants

4

Reactant 2

HCID 18525843Methyl 2-(piperidin-1-yl)pyridine-4-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 18525842[2-(Piperidin-1-yl)pyridin-4-yl]methanolYield 65.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of LAH (5.5 g, 0.145 mol) in dry THF (500 mL) at 0° C. was added methyl 2-piperidin-1-ylisonicotinate (18 g, 0.095 mol) in dry THF (100 mL) under N2 atmosphere. The reaction mixture was stirred at RT for 4 h and quenched with 10% aqueous NaOH solution at −20° C. The solid was filtered off, washed with THF and concentrated. The residue was dissolved in CH2Cl2 (250 mL), washed with water, brine and dried. The solvent was removed under vacuum and the crude was purified by column chromatography over silica gel (CHCl3/MeOH, 9:1) to give (2-piperidin-1-yl pyridin-4-yl)methanol (12 g, 65%). 1H NMR (DMSO-d6) δ 7.98 (d, J=5.2 Hz, 1H), 6.71 (s, 1H), 6.51 (br d, 1H), 5.24 (t, J=5.2 Hz, 1H), 4.41 (d, J=5.2 Hz, 2H), 3.49-3.46 (m, 4H), 1.58-1.50 (m, 6H).

Workup

  1. customquenched with 10% aqueous NaOH solution at −20° C
  2. filtrationThe solid was filtered off
  3. washwashed with THF
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in CH2Cl2 (250 mL)
  6. washwashed with water, brine
  7. customdried
  8. customThe solvent was removed under vacuum
  9. customthe crude was purified by column chromatography over silica gel (CHCl3/MeOH, 9:1)

Sources & evidence

ORD record
ord-ef43a2b0866d40839e76d95162fe3c53
Source dataset
uspto-grants-2010_11
Patent number
US07838522B2

Reaction notes

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