反应详情

To a solution of 4-iodoaniline (4.618 g, 21.1 mmol) and 2-chloro-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (5.33 g, 22.1 mmol) in 100 mL methylene chloride was added magnesium sulfate (25.38 g, 211 mmol). The reaction mixture was stirred at room temperature overnight. The magnesium sulfate was filtered off and additional magnesium sulfate (26 g) was added to the filtrate. The reaction mixture was stirred at room temperature for 3 days. The magnesium sulfate was filtered off and additional magnesium sulfate (40 g) was added to the filtrate. The reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered and concentrated in vacuo. The resulting residue was dissolved in 50 mL of toluene and was heated to reflux for 3 hr., then was stirred at room temperature overnight. The toluene was removed in vacuo and the residue was crystallized from methanol/ethanol/methylene chloride. The crystalline product (9.07 g) was dissolved in 150 mL methylene chloride and 30 mL methanol and was treated with sodium borohydride (3.90 g, 103 mmol) which was added in portions. The reaction was stirred at room temperature overnight at which time saturated aqueous sodium bicarbonate was added. The mixture was extracted with methylene chloride and the organic layer was dried (magnesium sulfate), filtered, and concentrated. Medium pressure silica gel chromatography of the residue (1:1 methylene chloride:hexanes) afforded 5.97 g (64%) of the title compound of Step A.

1. filtrationThe magnesium sulfate was filtered off
2. additionadditional magnesium sulfate (26 g) was added to the filtrate
3. stirringThe reaction mixture was stirred at room temperature for 3 days
4. filtrationThe magnesium sulfate was filtered off
5. additionadditional magnesium sulfate (40 g) was added to the filtrate
6. stirringThe reaction mixture was stirred at room temperature overnight
7. filtrationThe reaction mixture was filtered
8. concentrationconcentrated in vacuo
9. dissolutionThe resulting residue was dissolved in 50 mL of toluene
10. temperaturewas heated
11. temperatureto reflux for 3 hr
12. stirring, then was stirred at room temperature overnight
13. customThe toluene was removed in vacuo
14. customthe residue was crystallized from methanol/ethanol/methylene chloride
15. dissolutionThe crystalline product (9.07 g) was dissolved in 150 mL methylene chloride
16. additionwas added in portions
17. additionwas added
18. extractionThe mixture was extracted with methylene chloride
19. dry with materialthe organic layer was dried (magnesium sulfate)
20. filtrationfiltered
21. concentrationconcentrated