反应详情

温度

-78 °C

To a solution of 2′-chloroacetophenone (1-1) (1.26 mL, 9.70 mmol) in 40 mL of THF at −78° C. was slowly added 10.7 mL (10.7 mmol) of a 1M LiHMDS solution in THF. After stirring for 1 h at −78° C., a solution of 2.05 g (9.70 mmol) of 3-benzyloxy-benzaldehyde (1-2) in 8 mL of THF was added, and stirring was continued at that temperature for an additional hour. The mixture was then dumped into a separatory funnel containing 100 mL of saturated aqueous NH4Cl and extracted twice with 100 mL of EtOAc. The organic phases were combined, washed with 100 mL of brine, and dried over Na2SO4. After filtering off the drying agent, the solvent was removed on a rotary evaporator, and the residue was dissolved in 50 mL of CH2Cl2. After cooling to −78° C., 4 mL of triethylamine and 2 mL of trifluoroacetic anhydride were added sequentially, and the mixture was allowed to warm to rt and stir for 12 h. The reaction was then dumped into a separatory funnel with 100 mL of 1M HCl, the layers were separated, and the aqueous phase extracted again with CH2Cl2. The organic layers were combined, washed again with 1 M HCl, washed with water, and dried over Na2SO4. After concentration, the crude material was purified by chromatography on silica gel with a gradient of 0 to 40% EtOAc in hexanes over 45 min to provide 1-4 as a viscous yellow oil. Data for 1-4: 1HNMR (500 MHz, CDCl3) δ 7.5-7.0 (m, 15H) 5.1 (s, 2H) ppm.

1. customat −78° C.
2. stirringstirring
3. waitwas continued at that temperature for an additional hour
4. customThe mixture was then dumped into a separatory funnel
5. extractionextracted twice with 100 mL of EtOAc
6. washwashed with 100 mL of brine
7. dry with materialdried over Na2SO4
8. filtrationAfter filtering off the drying agent
9. customthe solvent was removed on a rotary evaporator
10. dissolutionthe residue was dissolved in 50 mL of CH2Cl2
11. temperatureAfter cooling to −78° C.
12. addition4 mL of triethylamine and 2 mL of trifluoroacetic anhydride were added sequentially
13. temperatureto warm to rt
14. stirringstir for 12 h
15. customThe reaction was then dumped into a separatory funnel with 100 mL of 1M HCl
16. customthe layers were separated
17. extractionthe aqueous phase extracted again with CH2Cl2
18. washwashed again with 1 M HCl
19. washwashed with water
20. dry with materialdried over Na2SO4
21. concentrationAfter concentration
22. customthe crude material was purified by chromatography on silica gel with a gradient of 0 to 40% EtOAc in hexanes over 45 min