Yield:55265-53-7 90.5%

Reaction Conditions:

with ammonia in tetrahydrofuran; for 0.283333 h;

Steps:

14

Under argon, oxalyl chloride (25 mL, 36 g, 290 mmol, 2.0 equiv) was added to a suspension of 2-dimethyl-3-dimethyl-cyclopropanecarboxylic acid (20.24 g, 142.3 mmol, 1 equiv) in dichloromethane (50 mL) over a period of 3 minutes. The reaction mixture showed vigorous gas evolution. The reaction mixture was stirred at 20° C. for 45 minutes (gas evolution ceased after 40 minutes). Dichloromethane and oxalyl chloride were distilled at 27° C.-57° C. through a short-path distillation apparatus. The product was sublimed on a Kugelrohr apparatus. Two cuts were taken. The initial cut (18° C., 15 mtorr) gave 4.91 g (21.5% yield) of product, an intermediate acid chloride, as white crystalline needles with a small amount of a free-flowing colorless liquid. The second cut (18° C.-60° C., 15 mtorr) gave 16.13 g (70.5%) of the product as white crystalline needles. ¹H NMR showed the second cut to be much purer than the first cut. Ammonia gas was bubbled through a solution of the intermediate acid chloride (10.35 g, 64.43 mmol) in anhydrous THF (200 mL) for 2 minutes. The reaction mixture was then capped and stirred for 15 minutes. The precipitated ammonium chloride was then filtered twice through paper. The filtrate was rotary evaporated (20° C.) giving 8.23 g (90.5% yield) of product as a white crystalline solid. This material was dissolved in warm EtOAc (15 mL), and hexanes (60 mL) were added. The crystallizing solution was allowed to stand at 20° C. for 1 hour. The resultant crystals were filtered, washed with hexanes (1×25 mL), and dried under high vacuum (125 mtorr) for 48 hours to yield Compound X as a white, finely crystalline solid.

References:

US2006/25477,2006,A1 Location in patent:Page/Page column 8