Oxalyl chloride → HCID 178451075, compound

Participants

Reaction Steps

0.330 g of trans-4-(4-tert-butoxycarbonylmethylcyclohexyl)benzoic acid is placed in 10 mL of dichloromethane with stirring, at room temperature, under a nitrogen atmosphere. 0.12 mL of oxalyl chloride (1.42 mmol, 1.4 eq.) and 2 drops of dimethylformamide are successively added. The reaction medium is stirred for 2 hours and concentrated under vacuum. The tert-butyl trans-4-(4-chlorocarbonylphenyl)cyclohexaneacetate formed is dissolved in 8 mL of acetonitrile and placed under nitrogen. The mixture is cooled in an ice bath and 0.17 g of potassium thiocyanate (1.75 mmol, 1.7 eq.) is added. The reaction mixture is stirred at room temperature for 1 hour 30 minutes. 0.380 g of cyclopentyloxyacetic acid hydrazide (2.40 mmol, 2.32 eq.) dissolved in 5 mL of acetonitrile is then added and the mixture is refluxed for 2 hours 30 minutes and then left to stand at room temperature for 36 hours. The precipitate formed is filtered off and washed with acetonitrile. The filtrate is diluted with dichloromethane and washed with water. The organic phase is dried over sodium sulfate and concentrated under vacuum. The residue is dissolved in 5 mL of dichloromethane; 3 mL of trifluoroacetic acid are added and the reaction medium is stirred for 1 hour 30 minutes and concentrated under vacuum. After triturating in methanol, ethanol and ethyl acetate, the residue is chromatographed on silica gel, eluting with a gradient of methanol in dichloromethane ranging from 3% to 5%. After triturating in ethanol, 0.070 g of trans-{4-[4-(5-cyclopentyloxymethyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenyl]cyclohexyl}acetic acid is obtained.

Provenance & Evidence