Water → 1-(2-Chloro-6-methylpyridin-3-yl)cyclobutanol

Temperatur

-15 °C

A suspension of molecular sieves (4 Å) and 3-bromo-2-chloro-6-methylpyridine (CAN 185017-72-5, 5 g, 24.2 mmol) in THF (50 mL) was cooled to −15° C. 1.3 M isopropyl magnesium chloride lithium chloride complex solution in THF (19.6 mL, 25.4 mmol) was added within 30 min. Stirring was continued for 1 h at −15° C. Cyclobutanone (1.87 g, 2.00 mL, 26.6 mmol) was slowly added. Stirring was continued for 2 h at −15° C. and for further 2 h at 0° C. Water (2.5 mL) was added, the mixture was concentrated in vacuo, and poured onto sat. aqueous NH4Cl solution. The mixture was extracted with EtOAc (2×100 mL). The combined extracts were washed with ice water (50 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 140 g, heptane/EtOAc 0-40% in 120 min.) to give the title compound (3.33 g, 70%) as white solid, MS (ESI): m/e=198.1 [MH+].

1. stirringStirring
2. waitwas continued for 2 h at −15° C. and for further 2 h at 0° C
3. concentrationthe mixture was concentrated in vacuo
4. additionpoured onto sat. aqueous NH4Cl solution
5. extractionThe mixture was extracted with EtOAc (2×100 mL)
6. washThe combined extracts were washed with ice water (50 mL)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash chromatography (silica gel, 140 g, heptane/EtOAc 0-40% in 120 min.)

ORD-Eintrag

ord-e5f9a3eec92e42abb728a38ac7960323

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09303012B2