Isopropyl Acetate → (2S,4R)-4-(2-Trifluoromethyl-benzenesulfonyl)-1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-pyrrolidine-2-carboxylic Acid (1-cyano-cyclopropyl)-amide

Participants

Reaction Conditions

Reaction Steps

(2S,4R)-4-(2-Trifluoromethyl-benzenesulfonyl)-1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-pyrrolidine-2-carboxylic acid methyl ester Potassium fluoride (26 mg, 445 umol) and triethylamine (62 ul, 445 umol) were added to a solution of (2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl ester (50 mg, 148 umol; prepared as described for the corresponding (2S,4S)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid ethyl ester in example 192e) and 2-chloro-5-trifluoromethyl-[1,3,4]thiadiazole (31 mg, 163 umol; CAS Reg. No. 53645-98-0) in N,N-dimethylacetamide (1 ml). The reaction mixture was heated in a microwave oven to 120° C. for 90 min. Ice water/0.1 N aqueous HCl solution 1/1 and iPrOAc were added and the layers were separated. The aqueous layer was extracted one more time with iPrOAc, the combined organic layers were washed with ice water/brine 1/1 and dried over Na2SO4. The solvent was removed under reduced pressure to give the title compound as yellow solid (50 mg, 102 umol; 69%) which was sufficiently pure to be used in the next reaction step. MS (ESI): m/z=558.2 [M+H]+.

Provenance & Evidence