反应详情

A solution of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(1-oxidopyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (0.465 g, 0.835 mmol) in trifluorotoluene (15 ml) was cooled to 0° C. Cumylamine (0.282 mL, 2.09 mmol) was added, followed by p-toluenesulfonic anhydride (0.273 g, 0.835 mmol) in 2 portions, 5 minutes apart. After 10 minutes, additional cumylamine (0.282 mL, 2.09 mmol) was added, followed by p-toluenesulfonic anhydride (0.273 g, 0.835 mmol) in 2 portions, 5 minutes apart. After 10 minutes, a third addition of cumylamine (0.282 mL, 2.088 mmol) was carried out, followed by p-toluenesulfonic anhydride (273 mg, 0.835 mmol) in 2 portions, 5 minutes apart. After 10 hours, the reaction was diluted with EtOAc (250 mL) and washed with water (2×50 mL) and brine (50 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography with 0-100% EtOAc/hexanes to afford tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (349.1 mg, 62%). LC-MS=674.4 (M+1)+. 1H NMR (600 MHz, CD3OD) δ −0.07 (s, 3H), 0.07 (s, 3H), 0.88 (s, 9H), 1.15-1.92 (m, 20H), 2.75 & 2.46 (2 multiplets, 1H), 3.87 (m, 4H), 4.06 (bs, 1H), 5.31 & 5.12 (2 singlets, 1H), 6.00-6.10 (m, 1H), 7.07 (m, 5H), 7.23 (bs, 1H), 7.36 (bs, 2H), 7.81 (bs, 1H), 7.90 (m, 2H).

1. waitAfter 10 minutes
2. waitAfter 10 hours
3. washwashed with water (2×50 mL) and brine (50 mL)
4. dry with materialThe organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by silica gel chromatography with 0-100% EtOAc/hexanes