5-Cyclohexylisoxazole-3-carboxylic acid synthesis

Yield:908856-66-6 90%

Reaction Conditions:

Stage #1: ethyl 5-cyclohexylisoxazole-3-carboxylatewith sodium hydroxide in ethanol;water at 20;
Stage #2: with hydrogenchloride in ethanol;water; pH=3 - 4;

Steps:

Synthesis of 5-cyclohexyl-isoxazole-3-carboxylic acid (55)

Synthesis of 5-cyclohexyl-isoxazole-3-carboxylic acid (55) A solution of cyclohexyl isoxazole ethyl ester (51) (2.80 g, 12.5 mmol) in ethanol (30 mL) was stirred at room temperature. To this solution was added a 2M NaOH solution (9.4 mL, 18.8 mmol). Within a few minutes, precipitates were formed and reaction mixture became a thick paste. TLC showed that the reaction was complete. To the reaction mixture was added 0.5M HCl to adjust pH to 3-4, and then the mixture was extracted with ethyl acetate (2×100 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, and concentrated to afford 5-cyclohexyl-isoxazole-3-carboxylic acid (55) as white crystals (2.2 g. 90%). 55: ¹H NMR (500 MHz, CDCl₃): δ 9.60 (broad, 1H), 6.44 (s, 1H), 2.86 (m,1H), 2.08 (m, 2H), 1.83 (m, 2H), 1.74 (m, 1H), 1.50-1.28 (m, 5H).

References:

US2006/199853,2006,A1 Location in patent:Page/Page column 45