Methyl 6-methoxypyridine-3-carboxylate → (6-Methoxypyridin-3-yl)methanol

HRID 84301

Reaction equation

HRID 84301 reaction equation
[BH4-].[Na+].[CH3:3][O:4][C:5]1[CH:14]=[CH:13][C:8]([C:9](OC)=[O:10])=[CH:7][N:6]=1>C(O)C>[CH3:3][O:4][C:5]1[N:6]=[CH:7][C:8]([CH2:9][OH:10])=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 586039Methyl 6-methoxypyridine-3-carboxylateHCID 4311764Sodium borohydride

Product 1

HCID 12259941(6-Methoxypyridin-3-yl)methanol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium borohydride (11.30 g, 299 mmol) was added to a solution of the methyl 6-methoxynicotinate (5.00 g, 29.9 mmol) in ethanol (100 mL) at 0° C. The reaction was allowed to warm to room temperature and stirred for 3 days. The reaction was cooled to 0° C. and quenched by slow addition of 1 N HCl until pH 4.0. The reaction mixture was concentrated to remove ethanol. The remaining aqueous solution was washed with ethyl acetate (2×), then neutralized with saturated aqueous sodium bicarbonate, then extracted with ethyl acetate (3×). The organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated. The crude material was purified by silica chromatography (hexanes/ethyl acetate 1:1, 3:7) to give a clear oil. Mass/Yield-3.9 g/94% TLC (hexanes/ethyl acetate=1:1) Rf=0.22, UV active. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.91 (s, 3 H) 4.61 (s, 2 H) 6.68-6.77 (m, 1 H) 7.49-7.68 (m, 1 H) 8.09 (s, 1 H).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched by slow addition of 1 N HCl until pH 4.0
  3. concentrationThe reaction mixture was concentrated
  4. customto remove ethanol
  5. washThe remaining aqueous solution was washed with ethyl acetate (2×)
  6. extractionextracted with ethyl acetate (3×)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by silica chromatography (hexanes/ethyl acetate 1:1, 3:7)
  12. customto give a clear oil

Sources & evidence

ORD record
ord-bc4430b857004a0c8e893d490f6770e8
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Linked notes

Loading…