Water → HCID 66644972, compound

HRID 882820Notes

Reaction equation

HRID 882820 reaction equation
O[C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.Br[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19]([O-:22])([O-])=O.[Cs+].[Cs+].[OH2:25]>CN(C=O)C>[CH2:12]([O:25][C:8]([C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([O:22][CH2:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:7]=1)=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 178524392HCID 178524392, compound

Product 1

HCID 66644972HCID 66644972, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the suspension of 6-hydroxypicolinic acid (2500 mg, 17.97 mmol) in 37.75 ml of DMF were added (bromomethyl)benzene (6450 mg, 37.7 mmol) and Cs2CO3 (12300 mg, 37.7 mmol). The mixture was stirred overnight at room temperature (thin layer chromatography indicated nearly complete conversion with formation of two products, probably O- and N-alkylation). The reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic layers were successively washed with an aq. saturated NaHCO3 solution (2×), water, 10% citric acid solution (2×), and brine, dried over Na2SO4 and the solvent was removed under reduced pressure. Column chromatography on silica gel using dichloromethane/heptane (3:1) followed by dichloromethane and dichloromethane/MeOH (99:1) resulted in 6-benzyloxy-pyridine-2-carboxylic acid benzyl ester (3030 mg, 9.41 mmol, yield: 53%; ESI-MS [M+H]+=320.1) and 1-benzyl-6-oxo-1,6-dihydro-pyridine-2-carboxylic acid benzyl ester (containing minor impurities; 1920 mg, 6.01 mmol, yield: 34%; ESI-MS [M+H]+=320.1). The latter compound was hydrolyzed to the corresponding carboxylate by stirring in a solution of 10.3 ml of ethanol and 5.17 mL 2N of aq. NaOH at room temperature for 3 h. Water was added to the reaction mixture followed by extraction with ethyl acetate (3×). The aqueous layer was acidified to pH 3 using 2M HCl and then extracted three times with dichloromethane. The combined organic layers were washed with brine and dried over Na2SO4. Afterwards the solvent was removed under reduced pressure giving of the title product as a pale brown powder (1230 mg, yield: 89%).

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic layers were successively washed with an aq. saturated NaHCO3 solution (2×), water, 10% citric acid solution (2×), and brine
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-3dcd9331a57746b4bd4afbea8dd6d042
Source dataset
uspto-grants-2012_08
Patent number
US08236798B2

Reaction notes

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