4-(4-Chloro-2-fluorophenyl)nicotinaldehyde → (4-(4-Chloro-2-fluorophenyl)pyridin-3-yl)(cyclopropyl)methanol

Temperature

-78 °C

To a solution of 4-(4-chloro-2-fluorophenyl)nicotinaldehyde (1.6 g, 6.79 mmol) (prepared as in Example 5, Part B) in THF (32 mL) cooled to −78° C., was added cyclopropylmagnesium bromide (27.2 mL, 13.58 mmol) dropwise over a period of 20 min. The reaction mixture was allowed to stir at −78° C. for 3 h. The dry ice bath was removed and reaction mixture was brought to room temperature. The reaction mixture was quenched by addition of saturated aqueous ammonium chloride solution (30 mL). The reaction mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with brine (1×50 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (30% ethyl acetate in pet ether) to afford (4-(4-chloro-2-fluorophenyl)pyridin-3-yl)(cyclopropyl)methanol (900 mg, 3.24 mmol, 48% yield). LCMS (ESI) m/e 278.0 [(M+H)+, calcd for C15H14ClFNO 278.1]; LC/MS retention time (Method C): tR=1.62 min.

1. customThe dry ice bath was removed
2. customreaction mixture
3. customwas brought to room temperature
4. customThe reaction mixture was quenched by addition of saturated aqueous ammonium chloride solution (30 mL)
5. extractionThe reaction mixture was extracted with ethyl acetate (3×50 mL)
6. washThe combined organic extracts were washed with brine (1×50 mL)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe crude product was purified by silica gel chromatography (30% ethyl acetate in pet ether)

ORD record

ord-8dd77628f4924a2ca32a71a24e53a3e9

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969564B2