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

HRID 1514676Notes

Reaction equation

HRID 1514676 reaction equation
[H-].[Na+].[F: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.[Cl-].[NH4+]>C1COCC1.O>[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]([F: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

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 66643905[3-(4-Fluoro-phenyl)-5-((E)-styryl)-isoxazol-4-yl]-methanol

Product 1

HCID 667182126-[3-(4-Fluoro-phenyl)-5-((E)-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl esterYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (813 mg, 18.6 mmol) in 28 mL THF was added a solution of [3-(4-fluoro-phenyl)-5((E)-styryl)-isoxazol-4-yl]-methanol (5.00 g, 16.9 mmol) in THF (52 mL) and stirring was continued for 1 h at room temperature. A solution of methyl 6-chloronicotinate (3.26 g, 18.6 mmol) in THF (52 mL) was added. The mixture was stirred at room temperature for 3 h. Then water (50 mL) was added cautiously and then saturated ammonium chloride solution (150 mL) and water (100 mL). Extraction with ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:4 to 1:1) afforded the title compound (3.88 g, 94%) as a white solid. MS: m/e=431.3 [M+H]+.

Workup

  1. stirringThe mixture was stirred at room temperature for 3 h
  2. extractionExtraction with ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:4 to 1:1)

Sources & evidence

ORD record
ord-d893ab8653c2436598b3d9614faa9f62
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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