反应详情

To a solution of benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-1-ylcarbamate (6.73 mmol, 2.0 g) in DCM (15 ml) was added thionyl chloride (13.45 mmol, 0.0.98 mL) and the whole was stirred for 2 h at room temperature after which time LCMS suggested 100% conversion to product. The reaction mixture was concentrated under reduced pressure and the residue re-dissolved in DCM. This was repeated a further 4 times to give a light yellow solid. This was dissolved in DMF (25 mL) and ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (1.29 g, 6.17 mmol) was added followed by potassium carbonate (18.52 mmol, 2.56 g). The resulting suspension was heated to 60° C. and this temperature was maintained for 2 h after the reaction mixture was diluted with sat NH4Cl followed by water and the organics extracted with EtOAc (2×100 mL), dried (1PS paper) and concentrated under reduced pressure. The residue was then purified by flash chromatography (40% EtOAc/heptane) to give a white solid (2.54, 5.21 mmol, 84%). 1H NMR (400 MHz, CDCl3) δ 1.34 (t, 3H) 1.85 (m, 1H) 2.12 (m, 1H) 2.85 (m, 1H) 2.95 (m, 1H) 4.28 (q, 2H) 4.95 (d, 1H), 5.16 (s, 1H) 5.25 (m, 1H) 5.29 (s, 2H) 7.13 (brs, 2H) 7.35 (m, 6H), 7.87 (s, 1H).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue re-dissolved in DCM
3. customto give a light yellow solid
4. temperatureThe resulting suspension was heated to 60° C.
5. temperaturethis temperature was maintained for 2 h after the reaction mixture
6. extractionthe organics extracted with EtOAc (2×100 mL)
7. customdried (1PS paper)
8. concentrationconcentrated under reduced pressure
9. customThe residue was then purified by flash chromatography (40% EtOAc/heptane)
10. customto give a white solid (2.54, 5.21 mmol, 84%)