Lithium Hydroxide → HCID 28552056, compound

HRID 1630755Notes

Reaction equation

HRID 1630755 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](=[O:11])[N:7]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:6]=1)=[O:4].[OH-].[Li+]>O1CCCC1.CO>[CH3:20][O:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][N:7]2[C:8](=[O:11])[CH:9]=[CH:10][C:5]([C:3]([OH:4])=[O:2])=[CH:6]2)=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 10492471HCID 10492471, compound

Product 1

HCID 28552056HCID 28552056, compound

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of methyl coumalate (1 g, 6.49 mmol, 1 eq) in ethanol (30 mL) was added p-anisidine (0.79 g, 6.49 mmol, 1 eq). The reaction mixture was heated to reflux for 16 h. After this time, the solvent was removed under reduced pressure, and the residue was purified by column chromatography eluting with 3:2 ethyl acetate/hexane to afford 1-(4-methoxy-benzyl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid methyl ester. Mass Spec m/z=260 [M+H+]. To a solution of 1-(4-methoxy-benzyl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid methyl ester (400 mg, 1.54 mmol, 1 eq) in 3:1 tetrahydrofuran/methanol (20 mL) was added lithium hydroxide (148 mg, 6.17 mmol, 4 eq). The mixture was stirred at rt for 48 h then heated to 50° C. for 16 h. After this time, the mixture was concentrated under reduced pressure and partitioned between water and ethyl acetate. The aqueous layer was acidified with a 2N aqueous solution of hydrochloric acid then extracted with ethyl acetate. The organic layers were combined and washed with water, dried (MgSO4), filtered and concentrated under reduced pressure to afford 1-(4-methoxy-benzyl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid, which is used without further purification.

Workup

  1. temperaturethen heated to 50° C. for 16 h
  2. concentrationAfter this time, the mixture was concentrated under reduced pressure
  3. custompartitioned between water and ethyl acetate
  4. extractionthen extracted with ethyl acetate
  5. washwashed with water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4685f761a7ee47b6948b05184734adce
Source dataset
uspto-grants-2014_07
Patent number
US08791147B2

Reaction notes

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