Hydrochloric Acid → HCID 14305409, compound

Participants

Reaction Steps

To a stirred solution of 344 mls (0.74 mol) of 2.15 molar lithium diisopropyl amide (in hexanes) in 1.8 liters dry tetrahydrofuran cooled to -70° under nitrogen was added dropwise a solution of 65 g (0.67 mol) of 2-fluoropyridine in 300 mls dry tetrahydrofuran such that the temperature was maintained below -65°. After the solution was stirred 4 hours at -70°, 73.5 g (1.15 mol) of sulfur dioxide was added dropwise while the temperature was maintained below -65°. The suspension was stirred 1 hour at -70° and allowed to warm to room temperature. The reaction was diluted with ether and the precipitate was collected and washed with ether under a nitrogen atmosphere. The solid was stirred and dissolved in 550 mls acetic acid. 89 g (0.67 mol) of N-chlorosuccinimide was added portionwise while the temperature was maintained below 20°. After stirring an additional 30 minutes at room temperature, the reaction was evaporated, diluted with water, and extracted with ether. The combined organic layers were washed with saturated sodium bicarbonate solution until gas evolution ceased, dried over magnesium sulfate, and evaporated to a dark liquid which was dissolved in 900 mls methylene chloride and cooled to 0° under nitrogen. 244 g (3.3 mol) of t-butyl amine was added dropwise while the temperature was maintained below 10°. The reaction was stirred at room temperature for 20 hours and poured into water, acidified with 1 normal hydrochloric acid, and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to a dark liquid which was purified by flash chromatography to afford 56.3 g (36%) white solid: m.p. 95°-97°; NMR (CDCl3, 200 MHz), 1.25 (9H, s), 4.9 (NH), 7.3-7.4 (1H, m), 8.3-8.5 (2H, m); IR (nujol) 3290, 1590, 1570, 1320, 1160 cm-1.

Provenance & Evidence