Yield:-

Reaction Conditions:

with oxalyl dichloride in dichloromethane;N,N-dimethyl-formamide; for 2 h;

Steps:

8

5-(4-Chlorophenyl)isoxazole-3-carboxylic acid (0.120 g, .5 mmol) was allowed to stir in 15 mL Of CH₂Cl₂. Oxalyl chloride (.192ml, 1.5mmol) was added and the reaction was allowed to stir. Two drops of DMF were added via pipet and the effervescing reaction mixture was allowed to stir two additional hours. The reaction mixture was concentrated to dryness and residual oxalyl chloride was azeotroped using CH₂Cl₂ (3 x 20 ml). The resulting light-yellow solid was allowed to dry under vacuum for 4 hours. The solid was dissolved in 10 ml of CH₂CI₂, Intermediate E (0.100 g, 0.5 mmol) was added, and the reaction allowed to stir for 16 hours. LC/MS monitoring indicated reaction completion. The reaction was diluted with 20 mL of CH₂CI₂, washed with brine (3 x 20 mL) and subsequently dried over MgSO₄. Concentration to dryness yielded an off-white solid. Purification via Siθ₂ chromatography using a (9/0.9/0.1) mixture Of (CH₂CyCH₃OHZNH₃OH) afforded 34.2 mgs (20% yield) of the title compound as a white solid. ¹H NMR (300 MHz, CDCl₃) δ 7.72 (m, 2H), 7.45 (m, 2H), 7.25 (m, IH), 6.85 (m, 4H), 4.80 (d, 2H), 4.30 (m, IH), 3.10 (d, 3H), 2.68 (m, 2H), 2.30 (m, 5H), 1.98 (m, 2H), 1.83 (m, 2H).

References:

WO2007/78251,2007,A1 Location in patent:Page/Page column 41-42