Reaction #1775

Reaction equation

HCl

ethyl 2-methylnicotinate

diisobutylaluminum hydride

NaOH

→

3-Hydroxymethyl-2-methylpyridine

Solvents

toluene

THF

Conditions

Workup

1. 1
   Temperaturewarmed to ambient temperature
2. 2
   workup.WAITAfter 1 h
3. 3
   Temperaturethe solution was cooled in an ice bath
4. 4
   Otherto quench
5. 5
   Otherthe reaction
6. 6
   Filtrationfiltered
7. 7
   Concentrationthe solvents were concentrated under reduced pressure
8. 8
   OtherThe resulting aqueous solution was partitioned between CHCl3 and saturated aqueous NaHCO3
9. 9
   OtherThe organic layer was separated
10. 10
    Washthe aqueous layer was washed with additional CHCl3 (5×40 mL)
11. 11
    Dryingdried (MgSO4)
12. 12
    Otherevaporated under reduced pressure

Procedure

To a stirred solution of ethyl 2-methylnicotinate (1.50 g, 9.09 mmol) in freshly distilled THF (100 mL) at 0° C. was added diisobutylaluminum hydride (11.2 mL of a 1.5M solution in toluene, 16.9 mmol). The solution was stirred for 6 h at 0° C. and then warmed to ambient temperature. After 1 h, the solution was cooled in an ice bath and 1N HCl (75 mL) was added to quench the reaction. The mixture was made alkaline with aqueous NaOH (pH=8.5), filtered, and the solvents were concentrated under reduced pressure. The resulting aqueous solution was partitioned between CHCl3 and saturated aqueous NaHCO3. The organic layer was separated, and the aqueous layer was washed with additional CHCl3 (5×40 mL). The organic layers were combined, dried (MgSO4), and evaporated under reduced pressure. 3-Hydroxymethyl-2-methylpyridine was obtained as a slightly amber oil and was used in the next step without purification (TLC: Rf =0.40 (5% MeOH:CH2Cl2)).

Source