反应详情

A mixture of 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (10 g, 38.0 mmol), N,O-dimethylhydroxylamine hydrochloride (5.56 g, 57.0 mmol), and CH2Cl2 (120 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.92 g, 57.0 mmol) and 4-(dimethylamino)pyridine (0.464 g, 3.80 mmol). The mixture was cooled in an ice bath and treated with N,N-diisopropylethylamine (13.23 mL, 76 mmol) over 3 min. After 10 min, the cooling bath was removed and the mixture was stirred at RT overnight (˜14 h). The mixture was diluted with CH2Cl2 (150 mL), washed with saturated NaHCO3 (3×50 mL), 2 M HCl (2×50 mL) and brine, dried over MgSO4, and concentrated to provide a residue. The residue was purified by flash chromatography using a 120 g silica gel cartridge and 10:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give the title compound (7.8 g, 25.5 mmol, 67% yield) as a pale yellow oil. LC-MS: 307.1, (M+H)+. 1H-NMR (400 MHz, CDCl3) δ ppm 7.25-7.37 (5H, m), 5.11 (2H, s), 4.21 (2H, s), 3.66-3.71 (3H, m), 3.16 (3H, s), 2.83 (3H, d, J=5.93 Hz), 1.64-1.75 (4H, m).

1. temperatureThe mixture was cooled in an ice bath
2. customthe cooling bath was removed
3. additionThe mixture was diluted with CH2Cl2 (150 mL)
4. washwashed with saturated NaHCO3 (3×50 mL), 2 M HCl (2×50 mL) and brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated
7. customto provide a residue
8. customThe residue was purified by flash chromatography
9. washto elute the product
10. additionThe fractions containing the product
11. concentrationconcentrated on a rotary evaporator