反应详情

(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%).

1. concentrationAfter 45 min the mixture was concentrated
2. customthen azeotroped with DCM (4×10 mL)
3. customto give a yellow oil
4. temperatureThe mixture was heated to 60° C.
5. stirringwith stirring for 1 h
6. concentrationThe reaction was concentrated
7. customto remove DMF
8. custombefore partitioning between EtOAc/Water
9. additionThe phases were mixed
10. customseparated
11. washthe aqueous phase further washed with EtOAc (×2)
12. customCombined organics were dried
13. concentrationconcentrated
14. customto give a light yellow oil which
15. customwas purified on silica eluting with 25% EtOAc/heptane
16. customDesired fractions were collected
17. concentrationconcentrated