Sodium Hydroxide → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid

HRID 1516193Notes

Reaction equation

HRID 1516193 reaction equation
C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.[OH-].[Na+]>C(O)C>[CH3:17][C:16]1[O:15][N:14]=[C:13]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:12]=1[CH2:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:24])=[O:2])=[CH:5][N:6]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 665992926-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester

Product 1

HCID 665992136-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acidYield 45%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (3.89 g, 120 mmol) in ethanol (40 mL) was added aqueous sodium hydroxide (1 M, 36 mL, 36 mmol). The resulting mixture was heated under reflux for 2 h and then cooled to room temperature and concentrated. Addition of aqueous sodium hydroxide (1 M, 50 mL) was followed by washing with tert-butylmethylether (100 mL). The aqueous phase was acidified with aqueous hydrogen chloride (conc.) to pH=1 and extracted with tert-butylmethylether (100 mL). The organic layers was washed with water (50 mL) and aqueous sodium chloride (saturated, 50 mL). Drying over sodium sulfate and concentration afforded the title compound (1.68 g, 45%) as an off white solid. MS: m/e=309.3 [M−H]−.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 2 h
  3. concentrationconcentrated
  4. additionAddition of aqueous sodium hydroxide (1 M, 50 mL)
  5. washby washing with tert-butylmethylether (100 mL)
  6. extractionextracted with tert-butylmethylether (100 mL)
  7. washThe organic layers was washed with water (50 mL) and aqueous sodium chloride (saturated, 50 mL)
  8. dry with materialDrying over sodium sulfate and concentration

Sources & evidence

ORD record
ord-fd0b545bb5304a94b8c5034f21a4cec2
Source dataset
uspto-grants-2012_07
Patent number
US08227461B2

Reaction notes

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