Reaction #70459

Reaction equation

methyl 6-chloropyridine-3-carboxylate

ethyl magnesium bromide

→

solid

Yield 18.2%

1-(6-Chloropyridin-3-yl)cyclopropanol

Yield 18.2%

Solvents

ether

ether

Conditions

Workup

1. 1
   OtherThe mixture was quenched with saturated ammonium chloride aqueous solution and aqueous phase
2. 2
   OtherThe mixture was partitioned between DCM and brine
3. 3
   DryingThe organic layer was dried over Na2SO4
4. 4
   Concentrationconcentrated
5. 5
   Otherto afford the crude material
6. 6
   OtherThe resulting solid was purified by flash chromatography on silica gel
7. 7
   Washeluting with 10-80% EtOAc
8. 8
   workup.ADDITIONFractions containing the desired product
9. 9
   Concentrationconcentrated

Procedure

To a suspension of methyl 6-chloropyridine-3-carboxylate (1 g, 5.83 mmol) in 17 mL anhydrous ether was charged with 3 M ethyl magnesium bromide (8.5 mL, 26 mmol) in ether and stirred for 1 h before the addition of titanium isopropoxide (1.73 mL, 5.84 mmol) to the reaction mixture. The mixture was stirred for 16 h under nitrogen atmosphere. The mixture was quenched with saturated ammonium chloride aqueous solution and aqueous phase was adjusted to pH 3 with 1 N HCl. The mixture was partitioned between DCM and brine. The organic layer was dried over Na2SO4 and concentrated to afford the crude material. The resulting solid was purified by flash chromatography on silica gel, eluting with 10-80% EtOAc:heptane. Fractions containing the desired product were combined and concentrated to afford a brown greasy solid (180 mg, yield: 18.2%).

Source