Hydrochloric Acid → Ethyl 4-(hydroxymethyl)picolinate

HRID 1747062Notes

Reaction equation

HRID 1747062 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:9]=[CH:8][N:7]=1)=[O:5])[CH3:2].ClC(Cl)C.[BH4-].[Na+].Cl>C(O)C>[OH:13][CH2:12][C:10]1[CH:9]=[CH:8][N:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:11]=1.[OH:3][CH2:4][C:6]1[CH:11]=[C:10]([CH:9]=[CH:8][N:7]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 63651,1-DichloroethaneHCID 170509Diethyl 2,4-pyridinedicarboxylateHCID 4311764Sodium borohydride

Product 2

HCID 14541449Ethyl 4-(hydroxymethyl)picolinateHCID 19744774Ethyl 2-(hydroxymethyl)pyridine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 5 g of diethylpyridine-2,4-dicarboxylate were added 50 ml of ethanol and 50 ml of dichloroethane, followed by ice-cooling. 932 mg of sodium borohydride was added portionwise thereto, followed by stirring for 1 hour under ice-cooling, and further at room temperature for 15 hours. After ice-cooling the reaction solution, 5 ml of 6 M hydrochloric acid was added thereto, followed by stirring for 5 minutes and concentrating. A saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extracting with chloroform-isopropanol (10:1) and drying over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was purified by silica gel column chromatography (eluent:chloroform-methanol) to obtain 0.7 g of ethyl 4-(hydroxymethyl)pyridine-2-carboxylate (Production Example 53-1) and 1.6 g of ethyl 2-(hydroxymethyl)isonicotinate (Production Example 53-2), respectively.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. waitfurther at room temperature for 15 hours
  4. additionwas added
  5. stirringby stirring for 5 minutes
  6. concentrationconcentrating
  7. additionA saturated aqueous sodium hydrogen carbonate solution was added
  8. extractionby extracting with chloroform-isopropanol (10:1)
  9. dry with materialdrying over anhydrous magnesium sulfate
  10. concentrationAfter concentrating under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (eluent:chloroform-methanol)

Sources & evidence

ORD record
ord-38e130a590a24e93ba8735ab375ea3e3
Source dataset
uspto-grants-2015_10
Patent number
US09150541B2

Reaction notes

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