Cyclopropanecarboxaldehyde → (4-Chloro-3-methyl-2-pyridyl)-cyclopropyl-methanol

A solution of 2-bromo-3-methyl-4-chloro-pyridine (10.6 g, 57.1 mmol) in freshly distilled THF (120 mL) was cooled down to 0° C. and treated with isopropyl magnesium chloride (45.7 mL, 2.0 M in THF, 91.5 mmol). The resulting mixture was stirred at room temperature for 3 h then cooled to −5° C. Cyclopropane carboxaldehyde (6.83 mL, 91.5 mmol) was added. The reaction mixture was stirred at room temperature for 1 h and quenched by adding water (100 mL), and extracted with ethyl acetate (2×150 mL). The organic phase was separated, dried, and concentrated. The residue was purified by flash silica column chromatography (hexane:ethyl acetate, 3:1) to afford the title compound as a yellow oil (7.01 g, 62%). ESI-MS m/z: 198 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ ppm: 8.28 (d, J=5.4 Hz, 1H), 7.26 (d, J=5.4 Hz, 1H), 4.79 (d, J=5.4 Hz, 1H), 4.55 (br, s, 1H), 2.39 (s, 3H), 1.10-1.28 (m, 1H), 0.58-0.41 (m, 4H).

1. temperaturethen cooled to −5° C
2. stirringThe reaction mixture was stirred at room temperature for 1 h
3. customquenched
4. additionby adding water (100 mL)
5. extractionextracted with ethyl acetate (2×150 mL)
6. customThe organic phase was separated
7. customdried
8. concentrationconcentrated
9. customThe residue was purified by flash silica column chromatography (hexane:ethyl acetate, 3:1)

ORD record

ord-75ec7d96af9349948679814c27e44db3

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962842B2