反应详情

温度

60 °C

Ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 6) (62.4 mg, 0.28 mmol) was dissolved in DMF (5 mL), and Cs2CO3 (111 mg, 0.34 mmol), and 3 drops of water were added. 6-(2-bromoethoxy)-7-propyl-3-(trifluoromethyl)-1,2-benzisoxazole (100 mg, 0.28 mmol) was added and the reaction mixture was stirred for 10 h at 60° C. The solvent was removed under reduced pressure, and the crude product was taken up in EtOAc, filtered through silica gel, and the filtrate was concentrated under reduced pressure. The crude product was dissolved in THF (2 mL), and LiOH (0.5 M aqueous solution, 0.9 mL) and MeOH (4 drops) were added. After stirring for 18 h at 50° C. the reaction mixture was concentrated under reduced pressure. Water and HCl (1 N aqueous solution) were added until the mixture was acidic which was followed by extraction using EtOAc. The product was purified by silica gel filtration (gradient 1:6 EtOAc/Hexane to 100% EtOAc), yielding 12 mg (9% over 2 steps) of the title compound as white crystals. 1H NMR (300 MHz, CD3OD): δ 0.91 (t, 3H), 1.70 (m, 3H), 2.33 (m, 2H), 2.68 (m, 2H), 2.87 (m, 3H), 3.46 (m, 1H), 4.33 (m, 2H), 4.48 (m, 2H), 6.73 (dd, 1H), 6.82 (d, 1H), 7.11 (d, 1H), 7.34 (d, 1H), 7.67 (d, 1H).

1. customThe solvent was removed under reduced pressure
2. filtrationfiltered through silica gel
3. concentrationthe filtrate was concentrated under reduced pressure
4. dissolutionThe crude product was dissolved in THF (2 mL)
5. additionLiOH (0.5 M aqueous solution, 0.9 mL) and MeOH (4 drops) were added
6. stirringAfter stirring for 18 h at 50° C. the reaction mixture
7. concentrationwas concentrated under reduced pressure
8. additionWater and HCl (1 N aqueous solution) were added until the mixture
9. extractionwas followed by extraction
10. filtrationThe product was purified by silica gel filtration (gradient 1:6 EtOAc/Hexane to 100% EtOAc)