反应详情

(R)-Valine t-butyl ester (4.9 g; 28.28 mmol) was dissolved in methanol (100 ml). Acetic acid (1.62 ml; 28.28 mmol) and (1,3-dioxo-1,3-dihydroisoindol-2-yl)-acetaldehyde (5.40 g; 28.28 mmol) were added thereto. Then, sodium cyanoborohydride (1.95 g; 31.11 mmol) dissolved in THF (20 ml) was added. The mixture was stirred at RT for 6 h and then saturated NaHCO3 solution (200 ml) was added. Methanol was removed under reduced pressure, and the residue was extracted with EtOAc (3×; 100 ml). The combined organic phases were dried over MgSO4. Removal of the solvent under reduced pressure and purification of the residue by column chromatography (SiO′) resulted in t-butyl (R)-2-(2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethylamino)-3-methylbutyrate (6.60 g; 19.05 mmol). MS: 347.20 (M+H); Rt: 1.02 min (method: gradient 0 min 96% H2O (0.05% TFA) 2.0 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 4% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)

1. additionwas added
2. customMethanol was removed under reduced pressure
3. extractionthe residue was extracted with EtOAc (3×; 100 ml)
4. dry with materialThe combined organic phases were dried over MgSO4
5. customRemoval of the solvent
6. customunder reduced pressure and purification of the residue by column chromatography (SiO′)