Reaction #67631

Reaction equation

sodium

2-chloro-3-(difluoromethoxy)pyridine

methanol

methanol

→

3-(difluoromethoxy)-2-methoxypyridine

Yield 56.0%

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   OtherThe volatiles were removed under reduced pressure
3. 3
   Otherthe residue was partitioned between EtOAc and brine
4. 4
   ExtractionThe brine was extracted with EtOAc
5. 5
   Dryingthe combined organics were dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Otherthe volatiles removed under reduced pressure
8. 8
   OtherThe product was purified by silica gel chromatography (DCM)

Procedure

As shown in step 3-ii of Scheme 3, an excess of sodium metal was dissolved into 20 mL anhydrous methanol and 2-chloro-3-(difluoromethoxy)pyridine (2.0 g, 11.1 mmol) in anhydrous methanol was added. The reaction mixture was stirred in a sealed vessel at 100° C. for 6 hours. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and brine. The brine was extracted with EtOAc and the combined organics were dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography (DCM) to yield 3-(difluoromethoxy)-2-methoxypyridine as a colorless oil (Compound 1007, 1.1 g, 56% yield: ESMS (M+H) 176.

Source