反应详情

3-(2-amino-2-methylpropyl)benzoic acid methyl ester (Preparation 34) (1.36 g, 6.60 mmol), [2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol (Preparation 23) (2.96 g, 6.60 mmol), sodium iodide (980 mg, 6.60 mmol) and diisopropylethylamine (3.44 ml, 19.7 mmol) in acetonitrile (10 ml) were heated to reflux for 48 hours under a nitrogen atmosphere. The solvent was then removed in vacuo and saturated aqueous sodium hydrogen carbonate solution (20 ml) added and the product extracted with ethyl acetate (3×30 ml). The combined organics were washed with brine (3×20 ml), dried (sodium sulfate) and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume) to furnish the title compound, the purified product was dissolved in diethylether and evaporated (×3) to yield a white foam (1.70 g).

1. temperatureto reflux for 48 hours under a nitrogen atmosphere
2. customThe solvent was then removed in vacuo and saturated aqueous sodium hydrogen carbonate solution (20 ml)
3. additionadded
4. extractionthe product extracted with ethyl acetate (3×30 ml)
5. washThe combined organics were washed with brine (3×20 ml)
6. dry with materialdried (sodium sulfate)
7. customthe solvent removed in vacuo
8. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume)