Reaction #158295

Reaction equation

8-(3,4-dichlorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine

sodium hydride

(2-Bromoethoxy)(tert-butyl)dimethylsilane

→

title compound

2-{8-(3,4-dichlorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}ethanol

Solvents

DMF

water

Conditions

Workup

1. 1
   Temperaturecooling
2. 2
   workup.STIRRINGthe mixture was stirred at room temperature for 1 hr
3. 3
   Extractionthe mixture was extracted with ethyl acetate
4. 4
   WashThe extract was washed with saturated brine
5. 5
   Dryingdried over anhydrous magnesium sulfate
6. 6
   Otherthe solvent was evaporated under reduced pressure
7. 7
   workup.ADDITIONTo a mixture of the residue in THF (2 mL)
8. 8
   workup.ADDITIONwas added TBAF (1M THF solution, 439 μL)
9. 9
   workup.STIRRINGthe mixture was stirred at room temperature for 2 hr
10. 10
    workup.ADDITIONThe reaction mixture was diluted with water
11. 11
    Extractionthe mixture was extracted with ethyl acetate
12. 12
    WashThe extract was washed with saturated brine
13. 13
    Dryingdried over anhydrous magnesium sulfate
14. 14
    Otherthe solvent was evaporated under reduced pressure
15. 15
    OtherThe residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate)

Procedure

To a mixture of 8-(3,4-dichlorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine (200 mg) in DMF (5 mL) was added sodium hydride (60%, 31.6 mg) under ice-cooling, and the mixture was stirred for 30 min under a nitrogen atmosphere. (2-Bromoethoxy)(tert-butyl)dimethylsilane (113 μL) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a mixture of the residue in THF (2 mL) was added TBAF (1M THF solution, 439 μL), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) to give the title compound (26.9 mg).

Source