Reaction #1970

Reaction equation

4-t-butoxy-2,3,6-trifluoropyridine

LDA

hydrogen peroxide

sodium hydroxide

trimethoxyborane

→

title product

4-t-butoxy-2,3,6-trifluoro-5-hydroxypyridine

Solvents

acetic acid

THF

Conditions

Workup

1. 1
   workup.STIRRINGwith stirring for 25 min at -78° C
2. 2
   workup.STIRRINGthe mixture was stirred
3. 3
   Temperatureto warm to room temperature
4. 4
   Temperaturewhile cooling in an ice bath
5. 5
   workup.STIRRINGThe mixture was then stirred at room temperature for 16 hours
6. 6
   Otherquenched with saturated NH4Cl solution
7. 7
   ExtractionThe mixture was extracted with ether
8. 8
   Washthe extract was washed with brine
9. 9
   Dryingdried over MgSO4
10. 10
    OtherThe solvent was removed under vacuum
11. 11
    Otherthe residue was purified by flash chromatography on silica gel
12. 12
    Washeluting with 1:8 ethyl acetate
13. 13
    OtherRemoval of the solvent

Procedure

A 11.16 g (54.39 mmol) sample of 4-t-butoxy-2,3,6-trifluoropyridine, from Example 253 step b above, was dissolved in 50 mL of THF, and the solution was cooled to -78° C. To this solution was added LDA (65.6 mmol) with stirring for 30 min, during which a solid preciptated. To this mixture was added 7.5 mL of trimethoxyborane, with stirring for 25 min at -78° C. To this mixture was added 10 mL of acetic acid, and the mixture was stirred and allowed to warm to room temperature. Next was added 100 mL of 30% hydrogen peroxide and 100 mL of 2N sodium hydroxide while cooling in an ice bath. The mixture was then stirred at room temperature for 16 hours, and quenched with saturated NH4Cl solution. The mixture was extracted with ether, and the extract was washed with brine and dried over MgSO4. The solvent was removed under vacuum, and the residue was purified by flash chromatography on silica gel, eluting with 1:8 ethyl acetate:hexane. Removal of the solvent gave 9.769 g of the title product as a colorless liquid.

Source