4-(4-Chloro-2-fluorophenyl)nicotinaldehyde → 1-(4-(4-Chloro-2-fluorophenyl)pyridin-3-yl)ethanol

Temperature

-60 °C

To a solution of 4-(4-chloro-2-fluorophenyl)nicotinaldehyde (0.12 g, 0.509 mmol) (prepared as in Example 5, Part B) in anhydrous THF (15 mL) was added methyl magnesium bromide (3.0 M in diethyl ether) (0.364 g, 3.06 mmol) at −60° C. dropwise. After complete addition the solution was stirred at −60° C. for 10 min. The reaction mixture was then allowed to warm to room temperature and stirred for 1 h. The reaction was quenched by addition of saturated aqueous ammonium chloride solution (15 mL). The organics were extracted with ethyl acetate (3×20 mL) and washed with water (1×15 mL) and brine (1×15 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via preparative TLC (20% ethyl acetate in hexane) to afford 1-(4-(4-chloro-2-fluorophenyl)pyridin-3-yl)ethanol (40 mg, 0.159 mmol, 31% yield) as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H), 8.50 (s, 1H), 7.15-7.26 (m, 3H), 7.07 (d, J=3.8 Hz, 1H), 4.82 (q, J=6.3 Hz, 1H), 3.06 (bs, 1H), 1.40 (d, J=6.3 Hz, 3H).

1. additionAfter complete addition the solution
2. temperatureto warm to room temperature
3. stirringstirred for 1 h
4. customThe reaction was quenched by addition of saturated aqueous ammonium chloride solution (15 mL)
5. extractionThe organics were extracted with ethyl acetate (3×20 mL)
6. washwashed with water (1×15 mL) and brine (1×15 mL)
7. dry with materialThe combined organic extracts were dried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified via preparative TLC (20% ethyl acetate in hexane)

ORD record

ord-b469b59c291641c19d99d820ca05e1a4

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969564B2