Isopropyl Acetate → (2S,4R)-1-(2-Isopropyl-5-methyl-2H-pyrazol-3-yl)-4-[4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenesulfonyl]-pyrrolidine-2-carboxylic Acid Methyl Ester

Participants

Reaction Conditions

Reaction Steps

Lawesson's reagent (39 mg, 106 umol; CAS Reg. No. 19172-47-5) and isopropylhydrazine hydrochloride (12 mg, 106 umol; CAS Reg. No. 16726-41-3) were added to a solution of (2S,4R)-1-(3-oxo-butyryl)-4-[4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenesulfonyl]-pyrrolidine-2-carboxylic acid methyl ester and (2S,4R)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-1-(3-oxo-butyryl)-pyrrolidine-2-carboxylic acid methyl ester (50 mg, 96 umol) in tetrahydrofuran (2.9 ml) and pyridine (0.1 ml) under an argon atmosphere. The mixture was stirred for 16 h at 55° C. and for additional 48 h at ambient temperature. 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/10% aqueous sodium carbonate solution, ice water/brine 1/1 and dried over Na2SO4. The solvent was removed under reduced pressure to give a yellow oil which was purified by preparative thin layer chromatography (silica gel, iPrOAc/heptane) to obtain a mixture of the title compound and (2S,4R)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-1-(2-isopropyl-5-methyl-2H-pyrazol-3-yl)-pyrrolidine-2-carboxylic acid methyl ester (39 mg, 70 umol; 73%) as colorless oil. MS (ESI): m/z=558.2 [M+H]+.

Provenance & Evidence