Sodium hydride → HCID 131729833, compound

HRID 1514666Notes

Reaction equation

HRID 1514666 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:22])([CH3:21])[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]=1[CH2:19][OH:20])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].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:20][CH2:19][C:9]2[C:10]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[N:11][O:12][C:8]=2[C:7]([CH3:22])([CH3:21])[O:6][SiH2:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[N:27][CH:28]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 131729831HCID 131729831, compound

Product 1

HCID 131729833HCID 131729833, compoundYield 47.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of [5-(tert-butyl-dimethyl-silanyloxymethyl)-3-phenyl-isoxazol-4-yl]-methanol (4.09 g, 12.8 mmol) in THF (20 mL) was added dropwise to a suspension of sodium hydride (0.73 g of a 55% dispersion in mineral oil, 16.7 mmol). After stirring for 30 min at room temperature, the mixture was cooled in an ice bath and a solution of methyl 6-chloronicotinate (2.20 g, 12.8 mmol) in THF (20 mL) was added dropwise. The ice bath was removed and the reaction mixture was allowed to reach room temperature and was stirred for 2 h. After quenching with water and extractive workup (ethyl acetate/water) the organic phase was dried over sodium sulfate, filtered and concentrated. Chromatographic purification (silica, heptane:ethyl acetate=100:0 to 8:2) afforded the title compound as a colorless oil (2.76 g, 47%). MS: m/e=455.4 [M+H]+.

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. customThe ice bath was removed
  3. customto reach room temperature
  4. stirringwas stirred for 2 h
  5. customAfter quenching with water and extractive workup (ethyl acetate/water) the organic phase
  6. dry with materialwas dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customChromatographic purification (silica, heptane:ethyl acetate=100:0 to 8:2)

Sources & evidence

ORD record
ord-1caa33bd7eca47fd8267b96766e556dc
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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