Sodium Chloride → 6-[3-(2-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

HRID 1521053Notes

Reaction equation

HRID 1521053 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:14]([CH2:15][OH:16])=[C:13]([CH3:17])[O:12][N:11]=1.Cl[C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][N:20]=1.[Cl-].[Na+]>C1COCC1>[CH3:26][O:25][C:23](=[O:24])[C:22]1[CH:27]=[CH:28][C:19]([O:16][CH2:15][C:14]2[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[F:3])=[N:11][O:12][C:13]=2[CH3:17])=[N:20][CH:21]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 68444673(3-(2-Fluorophenyl)-5-methylisoxazol-4-yl)methanol

Product 1

HCID 684455236-[3-(2-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl esterYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (55% dispersion in mineral oil, 1.16 g, 26.5 mmol) in THF (30 mL) was added a solution of [3-(2-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-methanol (5.0 g, 24.1 mmol) in THF (60 mL) at 0° C. and the reaction mixture warmed to room temperature over 30 min. Then a solution of methyl 6-chloronicotinate (4.65 g, 26.5 mmol) in THF (60 mL) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then poured into aqueous sodium chloride (saturated) and the mixture was extracted with ethyl acetate. The combined organic layers were then washed with water and brine and then dried over sodium sulfate, filtered and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=4:1 to 2:1) afforded the title compound (4.0 g, 49%) which was obtained as a white solid. MS: m/e=343.0 [M+H]+.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layers were then washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by chromatography (SiO2, heptane:ethyl acetate=4:1 to 2:1)

Sources & evidence

ORD record
ord-f5d8a93e5abb461189cf303243aca080
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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