反应详情

A solution of 24 (4.3 g, 9.03 mmol) in a mixture of TFA (60 ml) and water (20 ml) was kept at room temperature for 2 days until almost no starting 24 was seen by HPLC analysis. The reaction was concentrated, co-evaporated with acetionitrile (3×100 ml) to remove most of TFA and water and re-dissolved in THF (100 ml), triethylamine (2 ml) was added to neutralize residual TFA followed by 12 ml of 1 M tetrabutylammonium fluoride in THF. The reaction was allowed to proceed for 2 hrs (monitored by HPLC), concentrated and treated with water (70 ml) and ethyl acetate. At this point crystallization of 25 started as a gelatinous solid. After being allowed the solid to form for several hours the mixture was filtered to collect the solid, which was washed with 33% ethyl acetate in hexane and dried to afford 1.65 g of 25. The aqueous phase was extracted with ethyl acetate. All ethyl acetate extracts, including the very first one, were combined, concentrated and chromatographed on silica in a gradient of MeOH (10-20%) in dichloromethane to afford 0.75 g of 25 (combined yield—2.4 g, 77%). 1H NMR (DMSO-d6): δ 10.53 (s, 1H), 7.57 (s, 1H), 7.30 (m, 5H), 6.42 (s, 2H), 4.80 (d, J=4.8 Hz, 1H), 4.36 (d, J=1.5 Hz, 2H), 4.11 (m, 1H), 3.99 (m, 1H), 3.67 (m, 1H), 3.32 (m, 2H), 2.10 (m, 1H), 1.09 (d, J=6.3 Hz, 3H).

1. concentrationThe reaction was concentrated, co-evaporated with acetionitrile (3×100 ml)
2. customto remove most of TFA and water
3. dissolutionre-dissolved in THF (100 ml)
4. additiontriethylamine (2 ml) was added
5. waitto proceed for 2 hrs
6. concentration(monitored by HPLC), concentrated
7. additiontreated with water (70 ml) and ethyl acetate
8. customAt this point crystallization of 25
9. customto form for several hours the mixture
10. filtrationwas filtered
11. customto collect the solid, which
12. washwas washed with 33% ethyl acetate in hexane
13. customdried