反应详情

温度

90 °C

Thionyl chloride (4 mL) was added to a solution of 1-[1-(ethoxycarbonyl)azepan-4-yl]-4-fluoropiperidine-4-carboxylic acid (1.24 g, assume 3.92 mmol) and the reaction was stirred at 90° C. for 3 h. The reaction mixture was cooled to rt and concentrated in vacuo. DCM (4 mL) was added to a portion of the residue (0.65 mmol) followed by tert-butylamine (0.14 mL, 1.31 mmol) and DIPEA (0.57 ml, 3.27 mmol), the reaction mixture was stirred at rt for 48 h. The solvents were removed in vacuo, and the residue was partitioned between DCM (50 mL) and sat. NaHCO3 sol. (25 mL), organic layer washed with sat. NaCl sol. (25 mL) and dried over MgSO4. The residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 Å, 25 mL per min, gradient 0% to 7% MeOH in DCM]) to give ethyl 4-(4-fluoro-4-((tert-butyl)carbamoyl)piperidin-1-yl)azepane-1-carboxylate (0.11 g, 46.8%) as a yellow oil.

1. temperatureThe reaction mixture was cooled to rt
2. concentrationconcentrated in vacuo
3. stirringthe reaction mixture was stirred at rt for 48 h
4. customThe solvents were removed in vacuo
5. customthe residue was partitioned between DCM (50 mL) and sat. NaHCO3 sol. (25 mL), organic layer
6. washwashed with sat. NaCl sol. (25 mL)
7. dry with materialdried over MgSO4
8. customThe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 Å, 25 mL per min, gradient 0% to 7% MeOH in DCM])