Sodium hydride → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester

HRID 1516191Notes

Reaction equation

HRID 1516191 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][OH:14].[H-].[Na+].Cl[C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=1>C1COCC1.C(OCC)(=O)C>[CH3:25][O:24][C:22](=[O:23])[C:21]1[CH:26]=[CH:27][C:18]([O:14][CH2:13][C:3]2[C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:5][O:6][C:2]=2[CH3:1])=[N:19][CH:20]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 2776149(5-Methyl-3-phenyl-1,2-oxazol-4-yl)methanol

Product 1

HCID 665992926-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl esterYield 42.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (263 mg, 1.39 mmol) in THF (3 mL) was added sodium hydride (55% dispersion in mineral oil, 66.7 mg, 1.53 mmol). After stirring for 15 min at room temperature methyl 6-chloronicotinate (286 mg, 1.67 mmol) was added and the reaction mixture was stirred for 18 h. The mixture was then diluted with ethyl acetate (10 mL), washed with aqueous citric acid (10%, 10 mL), water (10 mL) and aqueous sodium chloride (saturated, 10 mL). The combined aqueous layers were extracted with ethyl acetate (10 mL) and the combined organic extracts dried over sodium sulfate. Filtration and concentration followed by purification by chromatography (silica, heptane:ethyl acetate 1:0 to 7:3) afforded the title compound (191 mg, 42%) as a colorless oil MS: m/e=325.3 [M+H]+.

Workup

  1. additionwas added
  2. washwashed with aqueous citric acid (10%, 10 mL), water (10 mL) and aqueous sodium chloride (saturated, 10 mL)
  3. extractionThe combined aqueous layers were extracted with ethyl acetate (10 mL)
  4. dry with materialthe combined organic extracts dried over sodium sulfate
  5. filtrationFiltration and concentration
  6. customfollowed by purification by chromatography (silica, heptane:ethyl acetate 1:0 to 7:3)

Sources & evidence

ORD record
ord-7e7ed472ed97404f97cacb2a6d85a153
Source dataset
uspto-grants-2012_07
Patent number
US08227461B2

Reaction notes

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