反应详情

温度

2.5 °C

To a mixture of (2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol (3.0 g, 10.9 mmol) and methylene chloride (30 ml), triethylamine (4.5 ml, 32.6 mmol) was added under a nitrogen stream, the resulting mixture was cooled to 0-5° C., and then a solution of 3,4,5-trimethoxybenzoyl chloride (2.6 g, 11.1 mmol) in methylene chloride (12 ml) was further added dropwise at below 10° C. After the reaction mixture was stirred at 0-5° C. for 30 minutes, dimethylaminopyridine (0.13 g, 1.1 mmol) was added at the same temperature. Subsequently, to the resulting mixture was added dropwise a solution of 4-chlorobenzenesulfonyl chloride (3.4 g, 16.3 mmol) in methylene chloride (12 ml) at below 10° C., and the resulting mixture was stirred at 0-5° C. for 4 hours. After completion of the reaction, to the reaction mixture was added water (30 ml), and the resulting mixture was partitioned. The separated organic layer was washed successively with 1N hydrochloric acid (30 ml), a 5% aqueous solution of sodium hydrogencarbonate (30 ml) and water (30 ml) and evaporated to dryness. Subsequently, to the residue obtained was added toluene to make the total volume 18 ml, and the resulting mixture was heated at 40° C. Furthermore, to the solution obtained was added methylcyclohexane (9 ml), and the resulting mixture was stirred at 40° C. for 30 minutes, and then at 0-5° C. for 30 minutes. The crystals precipitated were collected by filtration and dried at 50° C. in vacuo to afford the title compound [6.7 g, yield: 95.6%] as a pale yellow crystalline compound.

1. additionwas added under a nitrogen stream
2. stirringthe resulting mixture was stirred at 0-5° C. for 4 hours
3. customAfter completion of the reaction
4. customthe resulting mixture was partitioned
5. washThe separated organic layer was washed successively with 1N hydrochloric acid (30 ml)
6. customa 5% aqueous solution of sodium hydrogencarbonate (30 ml) and water (30 ml) and evaporated to dryness
7. customSubsequently, to the residue obtained
8. temperaturethe resulting mixture was heated at 40° C
9. customFurthermore, to the solution obtained
10. stirringthe resulting mixture was stirred at 40° C. for 30 minutes
11. waitat 0-5° C. for 30 minutes
12. customThe crystals precipitated
13. filtrationwere collected by filtration
14. customdried at 50° C. in vacuo