Potassium Carbonate → (R)-ethyl 1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

참여 물질

반응 단계

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (2.82 mmol, 760 mg) was dissolved in DCM (20 mL) and Thionyl Chloride (5.64 mmol, 0.409 mL, 671 mg) added and the solution stirred at room temperature. After 45 min the mixture was concentrated then azeotroped with DCM (4×10 mL) to give a yellow oil. To this oil was added DMF (10 mL) and potassium carbonate (8.46 mmol, 1170 mg) followed by ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.82 mmol, 587 mg). The mixture was heated to 60° C. with stirring for 1 h. The reaction was concentrated to remove DMF before partitioning between EtOAc/Water. The phases were mixed and separated and the aqueous phase further washed with EtOAc (×2). Combined organics were dried and concentrated to give a light yellow oil which was purified on silica eluting with 25% EtOAc/heptane. Desired fractions were collected and concentrated to give (R)-ethyl 1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate as a colourless solid (1.11 g, 86%).

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