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With palladium on carbon; hydrogen; In methanol; under 68404.6 Torr; for 24.0h; |
General procedure: A method similar to that of Example 1 was carried out. The starting material was 3-fluoroallylbenzene (1.36 g, 10 mmol) (R) -N-Boc-3-amino-4- (3-fluorophenyl) -butyric acid (1.78 g, 87% ee). The total yield was 60%.Allylbenzene (1.18 g, 10 mmol), Crotonaldehyde (1.4 g, 2 mmol) and Grubbs second-generation catalyst (9 mg, 0.01 mol, 0.1 mol%) Was dissolved in dichloromethane (20 mL) The reaction solution was cooled to 0 C for 12 hours; Hydroxylamine (1.59 g, 12 mmol) protected by Boc was added in turn followed by nitrogen atom, S configuration of oxygen is trimethylsilane protected alpha, alpha-diphenyl proline (330 mg, 1 mmol, 10 mol%) and p-nitrobenzoic acid (160 mg, 1 mmol, 10 mol%), The reaction mixture was stirred at 0 C for 15 hours. Removal of solvent methylene chloride; Acetonitrile (10 mL), Aqueous NaH2PO4 solution (240 mg NaH2PO4, 5 ml water) and H2O2 (35W% aqueous solution, 1.4 ml, 14 mmol) was added to the above residue; The reaction solution was added dropwise at 10 C to an aqueous solution of NaClO2 (1.27 g NaClO2, 14 mmol, 14 m water). After 3 hours, methylene chloride (20 ml) was added to dilute the reaction solution, The organic phase was washed with saturated sodium bicarbonate (5 ml) and Saturated sodium chloride (5 ml) was washed once and then dried over anhydrous sodium sulfate. Filtered and concentrated column chromatography (PE / EtOAc, 5: 1-3: 1) (R) -N-Boc-3-benzyl-5-hydroxyisoxazole (1.98 g, 71% yield), 92% ee. (R) -N-Boc-3-benzyl-5-hydroxyisoxazole (1.98 g, 7.1 mmol, 92% ee) was dissolved in methanol (50 mL) Pd / C (20% w / w, 550 mg) was added and hydrogenated at 90 atm for 24 hours. filter, (R) -N-Boc-3-amino-4-phenyl-butyric acid (1.96 g, 92% ee) to give a total yield of 70%. |