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

HRID 1475891Notes

Reaction equation

HRID 1475891 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 1N 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, 3H) 4.61 (s, 2H) 6.68-6.77 (m, 1H) 7.49-7.68 (m, 1H) 8.09 (s, 1H).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched by slow addition of 1N 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-c8d174aed914422cbe363fc0cda1304e
Source dataset
uspto-grants-2015_04
Patent number
US09018384B2

Reaction notes

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