反应详情

To a 5 L three neck flask fitted with a thermometer, mechanical stirrer, under argon was added 3 (108 g, 0.39 mol) and DMF (700 mL). To the light yellow solution was added imidazole (53 g, 0.78 mol) and TBDPSCl (tert-butyldiphenylchlorosilane) (150 mL, 0.58 mol). The solution turned cloudy and colorless. After stirring 18 hours the reaction was shown to be complete by TLC (EtOAc:hexanes; 3:7, anisaldehyde dip reagent). The clear yellow solution was concentrated under reduced pressure to a yellow residue (415 g). The residue was dissolved in diethyl ether (2 L) in a 4 L flask with a mechanical stirrer. To this solution was added 1.2M HCl (300 mL) to pH 3-4. The solution was stirred for 10 min. The layers were separated and the organic layer was washed with sat. NaHCO3 (300 mL) to pH 7 and brine (400 mL). The organic layer was dried over MgSO4 (60 g), filtered and concentrated under reduced pressure to 248 g of an oil. The oil was flashed chromatographed in portions over flash silica as follows. The oil (60 g) was flash chromatographed over flash silica gel (440 g) with anhydrous Na2SO4 (100 g) on top of the column packed with hexanes. Fractions of 500 mL were collected. Fractions 1-2 were eluted with hexanes, 3-10 with 4% ethyl acetate in hexanes, 11-18 with 10% ethyl acetate in hexanes. Fractions were monitored by TLC (EtOAc:hexanes; 2:8, anisaldehyde dip reagent) and HPLC. Fractions 9-18 were combined and concentrated under reduced pressure to give 37 g (18%) of product 4 as a viscous colorless oil. HPLC analysis showed a purity of 98%. The total weight of product 4 after purifications was 164 g (82%). 1H NMR (60 MHz, CDCl3) δ 7.0-7.7 (m, 10H), 3.2-5.2 (m, 9H), 1.0-2.0 (m, 24H).

1. concentrationThe clear yellow solution was concentrated under reduced pressure to a yellow residue (415 g)
2. dissolutionThe residue was dissolved in diethyl ether (2 L) in a 4 L flask with a mechanical stirrer
3. additionTo this solution was added 1.2M HCl (300 mL) to pH 3-4
4. stirringThe solution was stirred for 10 min
5. customThe layers were separated
6. washthe organic layer was washed with sat. NaHCO3 (300 mL) to pH 7 and brine (400 mL)
7. dry with materialThe organic layer was dried over MgSO4 (60 g)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure to 248 g of an oil
10. customThe oil was flashed chromatographed in portions over flash silica
11. customchromatographed over flash silica gel (440 g) with anhydrous Na2SO4 (100 g) on top of the column
12. customFractions of 500 mL were collected
13. washFractions 1-2 were eluted with hexanes, 3-10 with 4% ethyl acetate in hexanes, 11-18 with 10% ethyl acetate in hexanes
14. concentrationconcentrated under reduced pressure