反应详情

2-Methyl-4-bromo-aniline (930 mg, 5 mmol) was dissolved in DCE (50 mL); to this solution was transferred a solution of 4-(3-oxo-propyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (1.0 g, 5 mmol) in DCE (50 mL). The flask was submerged in a water bath at rt. To this clear solution was then added acetic acid (930 mg, 15.5 mmol, 3.1 equiv), followed by addition of powder NaBH(OAc)3 (3.18 g, 15 mmol, 3 equiv.) in 1 portion under N2 at r.t. The yellowish milky suspension was stirred at r.t. overnight. LC/MS showed m/z 372/370 at t=3.872 min. along with small amount of aniline starting material (MS: 186/188). TLC (5% of MeOH in DCM) showed no SM. of aldehyde, but aniline. The reaction was diluted with DCM (100 mL), cooled to ice-water bath, and quenched with 5 mL of conc. NH4OH (7.45M) in 150 mL of water. (2 M of NH4OH). The two layers were separated, and the aqueous layer was extracted with DCM (20 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (10 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The product was purified on a 25-g-silica gel column eluted with DCM to elute aniline; 2.5% MeOH in DCM for the product to get 0.85 g (46%) of the title compound as an oil.

1. customThe flask was submerged in a water bath at rt
2. customat t=3.872 min.
3. temperaturecooled to ice-water bath
4. customquenched with 5 mL of conc. NH4OH (7.45M) in 150 mL of water
5. customThe two layers were separated
6. extractionthe aqueous layer was extracted with DCM (20 mL×2)
7. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (10 mL)
8. dry with materialdried (anhydrous potassium carbonate)
9. filtrationfiltered
10. concentrationconcentrated
11. customThe product was purified on a 25-g-silica gel column
12. washeluted with DCM
13. washto elute aniline