反应详情

Protection of the phenol with dihydropyran was carried out based on the method given in Miyashita et al. (1977) J. Org. Chem. 42: 3772. Compound 1.1 (500 g, 2 mol) was dissolved in dichloromethane (4 L). 3,4-Dihydro-2H-pyran (250 g, 3 mol) was added to the suspension followed by PPTS (5 g, 20 mmol). The reaction mixture heated to a gentle reflux (3.5 h). HPLC showed ˜90% completion of the reaction. The reaction was concentrated under reduced pressure to ˜2 L of volume. 1 L of acetone was added, and 2 L of solvent was removed under reduced pressure. 1 L of acetone was added, and 1 L of solvent was removed under reduced pressure. 0.5 L of acetone was added, and 0.5 L of solvent was removed under reduced pressure. The resulting slurry of very fine, light yellow crystals was filtered and rinsed sequentially with two 500 mL portions of acetone. The product was dried in a vacuum oven at 50° C. until no further solvent collected in the traps. Compound 52.1 (528 g) was obtained as fine, light yellow crystals. 1H NMR (400 MHz)(DMSO-d6) δ 8.29 (s, 1H); 8.18 (d, 2H, J=8.9 Hz); 7.13 (d, 2H, J=8.9 Hz); 5.67 (m, 1H); 3.70 (m, 1H); 3.60 (m, 1H). 1.9-1.5 (m, 12H). MS ESI (pos.) m/e: 355.1 (M+Na).

1. temperatureThe reaction mixture heated to
2. temperaturea gentle reflux (3.5 h)
3. custom˜90% completion of the reaction
4. concentrationThe reaction was concentrated under reduced pressure to ˜2 L of volume
5. addition1 L of acetone was added
6. custom2 L of solvent was removed under reduced pressure
7. addition1 L of acetone was added
8. custom1 L of solvent was removed under reduced pressure
9. addition0.5 L of acetone was added
10. custom0.5 L of solvent was removed under reduced pressure
11. filtrationThe resulting slurry of very fine, light yellow crystals was filtered
12. washrinsed sequentially with two 500 mL portions of acetone
13. customThe product was dried in a vacuum oven at 50° C. until no further solvent
14. customcollected in the traps