Iodoethane → 4-Chloro-5-fluoro-2-propylpyridine

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (924 μL, 6.59 mmol) was dissolved in 9 mL of dry THF and the resultant solution was cooled to 0° C. in an ice bath. n-Butyllithium (3.07 mL of a 2.05M solution in THF, 6.29 mmol) was added via syringe to the amine solution and the resultant solution was stirred for 30 minutes at 0° C. The lithium diisopropylamide (LDA) solution was then cooled to -50° C. in an isopropyl alcohol/dry ice bath. To the cold LDA solution was added, dropwise from an addition funnel, over a 15 min period, a solution of 4-chloro-5-fluoro-2-picoline (435 μL, 3.0 mmol), the product of Example 64, in 9 mL of THF. The reaction solution turned dark orange-brown in color. The reaction solution was stirred at a temperature in the range -50° C. to -45° C. for 5 hours and then was cooled over a 15 min period to -78° C. Ethyl iodide (792 μL, 9.9 mmol) was added in one portion and the reaction solution was stirred at -78° C. for 20 min. The reaction was then quenched by pouring the reaction solution into 60 mL of 10% aqueous ammonium chloride solution. The aqueous mixture was extracted with 2 X 50 mL of methylene chloride. The combined organic extract was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo and the residue was distilledto afford the title compound, b.p. 80°-82° C. (12 mm Hg); MS DCI-NH3M/Z: 174 (M+H)+ 40%; 1H NMR (CDCl3) d 0.96 (t, 3H, J=7.5 Hz), 1.73 (spt, 2H, J=7.5 Hz), 2.73 (t, 2H, J=7.5 Hz), 7.21 (d, 1H, J=6.0 Hz), 8.38 (s, 1H).

Provenance & Evidence