反应详情

To a solution of (S)-2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2-methoxy-2-oxoethyl)-3-methyl-2-oxopiperidin-1-yl)butane-1-sulfonic acid (189.8 mg, 0.35 mmol; Example 372, Step B) in dichloromethane (5.0 mL) was added oxalyl chloride (0.061 mL, 0.70 mmol), followed by DMF (2 drops). The reaction was stirred at room temperature for 3.5 hours, then concentrated in vacuo. The sulfonyl chloride intermediate was dissolved in dichloromethane (5.0 mL), then treated with 3-oxetanamine (50.0 mg, 0.684 mmol; Pharmablock R & D Co. Ltd., Nanjing, China) and N,N-diisopropylethylamine (0.122 mL, 0.699 mmol). After stirring at room temperature for 16 hours, the reaction was quenched with methanol (2.0 mL), then concentrated in vacuo. Purification of the residue by chromatography on silica gel (4 g SiO2, 0%-50% EtOAc in hexanes) provided the title compound as a colorless oil.

1. concentrationconcentrated in vacuo
2. dissolutionThe sulfonyl chloride intermediate was dissolved in dichloromethane (5.0 mL)
3. stirringAfter stirring at room temperature for 16 hours
4. customthe reaction was quenched with methanol (2.0 mL)
5. concentrationconcentrated in vacuo
6. customPurification of the residue by chromatography on silica gel (4 g SiO2, 0%-50% EtOAc in hexanes)