Acetic Acid → (2-Chloro-6-methylpyridin-4-yl)methanol

HRID 1384585Notes

Reaction equation

HRID 1384585 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:13]=[C:12]([C:14](OCC)=[O:15])[CH:11]=[C:10]([CH3:19])[N:9]=1.C(O)(=O)C>C1COCC1>[Cl:7][C:8]1[CH:13]=[C:12]([CH2:14][OH:15])[CH:11]=[C:10]([CH3:19])[N:9]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 21226445Aluminium lithium hydrideHCID 22625009Ethyl 2-Chloro-6-methylisonicotinate

Product 1

HCID 22504306(2-Chloro-6-methylpyridin-4-yl)methanolYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Lithium aluminium hydride (350 mg, 9.26 mmol) was added in portions to a solution of ethyl 2-chloro-6-methyl-4-pyridinecarboxylate (1.85 g, 9.26 mmol) in THF (40 ml) cooled at 0° C. The mixture was stirred for 15 minutes at 0° C. and acetic acid (2 ml) was added. The mixture was partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH7.5 with 5 % aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with ethyl acetate/petroleum ether (35/65) to give 2-chloro-4-hydroxymethyl-6-methylpyridine (1.28 g, 88%). 1H NMR Spectrum: (CDCl3) 1.92(t, 1H); 2.53(s, 3H); 4.70(d, 2H); 7.06(s, 1H); 7.16(s, 1H) MS-ESI: 157 [MH]+

Workup

  1. customThe mixture was partitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed by evaporation
  6. customThe residue was purified by column chromatography
  7. washeluting with ethyl acetate/petroleum ether (35/65)

Sources & evidence

ORD record
ord-8dfc75f4244444e69acebfd68649fc1f
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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