反应详情

温度

60 °C

(R)-benzyl-5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate (5.08 mmol, 1.51 g) was dissolved in DCM (20 mL), thionyl chloride (10.16 mmol, 0.741 mL, 1.208 g) added and the resultant solution stirred at room temperature for 45 min. The sample was concentrated and azeotroped with DCM (×4). Potassium carbonate (15.23 mmol, 2.105 g) was added followed by DMF (20 mL) and (3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (5.08 mmol, 0.843 g) and the mixture heated to 60° C. for 1 h. The mixture was concentrated and partitioned between EtOAc/water. The aqueous layer was twice extracted with EtOAc and combined organics dried, filtered and concentrated to give a yellow oil which was purified on silica eluting with 0.5% MeOH/DCM to give (R)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate as a light coloured oil (1.74 g, 77%). 1H NMR (400 MHz, CDCl3) δ 1.83 (t, 1H) 2.79 (m, 2H) 3.27 (m, 2H) 4.52 (bs, 1H) 4.64 (d, 2H) 4.99 (bs, 1H) 5.09 (bs, 2H) 5.25 (s, 2H) 7.05-7.11 (m, 2H) 7.19 (m, 1H) 7.26-7.40 (m, 6H).

1. concentrationThe sample was concentrated
2. customazeotroped with DCM (×4)
3. concentrationThe mixture was concentrated
4. custompartitioned between EtOAc/water
5. extractionThe aqueous layer was twice extracted with EtOAc
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a yellow oil which
9. customwas purified on silica eluting with 0.5% MeOH/DCM