Methyl 6-chloropyridine-3-carboxylate → 1-(6-Chloropyridin-3-yl)cyclopropanol

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%).

1. customThe mixture was quenched with saturated ammonium chloride aqueous solution and aqueous phase
2. customThe mixture was partitioned between DCM and brine
3. dry with materialThe organic layer was dried over Na2SO4
4. concentrationconcentrated
5. customto afford the crude material
6. customThe resulting solid was purified by flash chromatography on silica gel
7. washeluting with 10-80% EtOAc
8. additionFractions containing the desired product
9. concentrationconcentrated

ORD-Eintrag

ord-33102e512a864b438aeb9c30f3223399

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08536168B2