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

HRID 872946
Notes
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Reaction equation

HRID 872946 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]([CH3:17])[O:12][N:11]=2)=[CH:6][CH:5]=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:7]3[CH:6]=[CH:5][C:4]([F:3])=[CH:9][CH:8]=3)=[N:11][O:12][C:13]=2[CH3:17])=[N:20][CH:21]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 28473136(3-(4-Fluorophenyl)-5-methylisoxazol-4-yl)methanol

Product 1

HCID 684447416-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (55% dispersion in mineral oil, 852 mg, 20 mmol) in THF (27 mL) was added a solution of [3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-methanol (103 mg, 0.55 mmol) (3.68 g, 18 mmol) in THF (54 mL) at 0° C. and the reaction mixture warmed to room temperature over 30 min. Then a solution of methyl 6-chloronicotinate (3.35 g, 20 mmol) in THF (1.5 mL) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature overnight. 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=7:3) afforded the title compound (81 mg, 47%) which was obtained as a light yellow solid. MS: m/e=343.3 [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=7:3)

Sources & evidence

ORD record
ord-7fd2674a4ab04a7cb709dc1a255da80b
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08975397B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes