Sodium hydride → 6-[3-(4-Chloro-phenyl)-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

HRID 1514694Notes

Reaction equation

HRID 1514694 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]([CH2:15][OH:16])=[C:13](/[CH:17]=[CH:18]/[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:12][N:11]=2)=[CH:6][CH:5]=1.Cl[C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][N:27]=1>C1COCC1>[CH3:33][O:32][C:30](=[O:31])[C:29]1[CH:34]=[CH:35][C:26]([O:16][CH2:15][C:14]2[C:10]([C:7]3[CH:6]=[CH:5][C:4]([Cl:3])=[CH:9][CH:8]=3)=[N:11][O:12][C:13]=2/[CH:17]=[CH:18]/[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:27][CH:28]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 66643814[3-(4-Chloro-phenyl)-5-([E]-styryl)-isoxazol-4-yl]-methanol

Product 1

HCID 667181406-[3-(4-Chloro-phenyl)-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (2.64 g, 60.5 mmol) in THF (100 mL) was added a solution of [3-(4-chloro-phenyl)-5-([E]-styryl)-isoxazol-4-yl]-methanol (17.2 g, 55.0 mmol) in THF (185 mL) at 0° C. The reaction mixture was stirred for 60 min at room temperature. A solution of methyl 6-chloronicotinate (10.6 g, 60.5 mmol) in THF (185 mL) was added at 0° C. The mixture was stirred at room temperature for 2 h and the product was extracted with ethyl acetate/aqueous ammonium chloride and ethyl acetate/brine. Chromatography (silica, ethyl acetate:heptane 2:8 to 7:3) afforded the title compound (15.6 g, 64%) as a white solid. MS: m/e (%)=446 (0.7, M+), 309 (47), 294 (28), 240 (26), 131 (100), 103 (51).

Workup

  1. stirringThe mixture was stirred at room temperature for 2 h
  2. extractionthe product was extracted with ethyl acetate/aqueous ammonium chloride and ethyl acetate/brine

Sources & evidence

ORD record
ord-225e9477e241484880fd32e92206c768
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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