Sodium hydride → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinonitrile

HRID 1520975Notes

Reaction equation

HRID 1520975 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:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][N:19]=1>C1COCC1.C(OCC)(=O)C>[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][O:14][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][N:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2776149(5-Methyl-3-phenyl-1,2-oxazol-4-yl)methanolHCID 51520946-Chloro-3-pyridinecarbonitrile

Product 1

HCID 684456176-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinonitrileYield 91%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (220 mg, 1.16 mmol) in THF (2 mL) was added sodium hydride (55% dispersion in mineral oil, 996 mg, 22.8 mmol). After stirring for 0.5 h at ambient temperature 6-chloronicotinonitrile (161 mg, 1.16 mmol) was added and the reaction mixture was stirred for 5 h at ambient temperature. It was 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). After drying over sodium sulfate and concentration purification by chromatography (SiO2, heptane:ethyl acetate=90:10 to 60:40) afforded the title compound (307 mg, 91%) as a white solid. MS: m/e=292.1 [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 materialAfter drying over sodium sulfate and concentration purification by chromatography (SiO2, heptane:ethyl acetate=90:10 to 60:40)

Sources & evidence

ORD record
ord-4dfa4700fe6f4246a27a2a3729ebfc42
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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