Water → (4-Chloro-3-methoxy-2-pyridyl)-cyclopropyl-methanol

Temperature

0 °C

2-bromo-4-chloro-3-methoxy-pyridine (2.97 g, 13.4 mmol) was added to THF (dry) (100 ml) and cooled to 0° C. Isopropylmagnesium chloride-lithium chloride complex (13.5 ml, 17.6 mmol) was added and the reaction mixture stirred for 0.5 h at room temperature. The mixture was cooled to 0° C., cyclopropanecarboxaldehyde (1.297 ml, 17.4 mmol) was added and the reaction mixture stirred for 1 h at room temperature. The mixture was cooled to 0° C., water (72.3 ml, 4 mol) was added and the reaction mixture stirred overnight at room temperature. The reaction mixture was extracted with ethyl acetate (3×75 mL), the organic phase dried over sodium sulfate, filtered and evaporated to dryness to obtain crude product which was purified over silica gel using 0:1 to 1:0 ethyl acetate in heptane to obtain (4-chloro-3-methoxy-2-pyridyl)-cyclopropyl-methanol as a yellow oil (2.4 g, 70%)

1. additionIsopropylmagnesium chloride-lithium chloride complex (13.5 ml, 17.6 mmol) was added
2. temperatureThe mixture was cooled to 0° C.
3. stirringthe reaction mixture stirred for 1 h at room temperature
4. temperatureThe mixture was cooled to 0° C.
5. stirringthe reaction mixture stirred overnight at room temperature
6. extractionThe reaction mixture was extracted with ethyl acetate (3×75 mL)
7. dry with materialthe organic phase dried over sodium sulfate
8. filtrationfiltered
9. customevaporated to dryness
10. customto obtain crude product which
11. customwas purified over silica gel using 0:1 to 1:0 ethyl acetate in heptane

ORD record

ord-6f5cd14a43234c639bf7b2b05812459f

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403818B2