反应详情

A round bottomed flask was charged with p-toluenesulfonyl chloride (1.85 g, 9.7 mmol, 2.2 equiv.) and 40 mL of DCM. The solution was cooled to an ice-water bath and evacuated and purged with nitrogen. To this solution was added a solution of 4-chloro-2-(2-hydroxy-ethyl)-N-(tetrahydro-pyran-4-yl)-benzamide (1.25 g, 4.4 mmol, 1 equiv.) in 40 mL of DCM, followed by triethylamine (1.5 ml, 11 mmol, 2.5 equiv.) and a few crystals of DMAP. The solution was stirred under nitrogen overnight from 0° C. to rt. TLC (5% MeOH in DCM for SM) showed the reaction was almost complete. LC/MS: 266 at 2.050 min; SM of 284 at 2.35 min. The reaction was quenched by addition of 1.6 g of polymer-supported ethyleneamine and stirred for 30 min. The reaction solution was filtered through a Celite pad, rinsed with DCM and concentrated to dryness. The residue was re-dissolved in 30 mL of DCM, washed with 10 mL of NaHCO3 aq. The aqueous layer was extracted with DCM (3×5 mL). The combined organic solutions were washed with brine (5 mL), dried (K2CO3), filtered and concentrated. The crude product was purified on a 50-g silica gel column, eluted with 2.5% 7N NH3 of MeOH in DCM to get 110 mg (10% yield) of the title compound as a light yellow solid.

1. temperatureThe solution was cooled to an ice-water bath
2. customevacuated
3. custompurged with nitrogen
4. waitLC/MS: 266 at 2.050 min
5. customThe reaction was quenched by addition of 1.6 g of polymer-supported ethyleneamine
6. stirringstirred for 30 min
7. filtrationThe reaction solution was filtered through a Celite pad
8. washrinsed with DCM
9. concentrationconcentrated to dryness
10. dissolutionThe residue was re-dissolved in 30 mL of DCM
11. washwashed with 10 mL of NaHCO3 aq. The aqueous layer
12. extractionwas extracted with DCM (3×5 mL)
13. washThe combined organic solutions were washed with brine (5 mL)
14. dry with materialdried (K2CO3)
15. filtrationfiltered
16. concentrationconcentrated
17. customThe crude product was purified on a 50-g silica gel column
18. washeluted with 2.5% 7N NH3 of MeOH in DCM