Methanol → Methyl 4-(hydroxymethyl)-6-methylpicolinate

HRID 2071153Notes

Reaction equation

HRID 2071153 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=C(C)[N:6]=[C:5]([C:10]#N)[CH:4]=1.CO.C[CH2:15][O:16][C:17]([CH3:19])=[O:18].C([O-])(O)=O.[Na+]>OS(O)(=O)=O.O>[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH3:10])[N:6]=[C:19]([C:17]([O:16][CH3:15])=[O:18])[CH:8]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 516892Sodium Bicarbonate2×HCID 591848654-(Hydroxymethyl)-6-methylpicolinonitrile

Product 1

HCID 68671851Methyl 4-(hydroxymethyl)-6-methylpicolinate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 440 mg of the 4-(hydroxymethyl)-6-methylpicolinonitrile in 3 mL of concentrated H2SO4 and 1.8 mL of H2O was stirred at 135° C. for 12 h. The temperature was decreased to 95° C., 6 mL of MeOH was added, and the solution was stirred at 95° C. for 1 h. The solution was added to ice with H2O and EtOAc. Solid NaHCO3 and sat. NaHCO3 solution were added to a pH=8. The aqueous layer was extracted with EtOAc (2×). The combined extracts washed with brine (40 mL), dried over Na2SO4, filtered and concentrated to give 393 mg of methyl 4-(hydroxymethyl)-6-methylpicolinate which was used without further purification.

Workup

  1. customwas decreased to 95° C.
  2. stirringthe solution was stirred at 95° C. for 1 h
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. washThe combined extracts washed with brine (40 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3878441ef8ab415fb649180ffa0d451b
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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