反应详情

2-Methyl-4-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-phenylamine (4.56 mmol) was dissolved in DCE (20 mL); to this solution was transferred a solution of 4-(2-Oxo-ethyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (0.85 g, 4.56 mmol) in DCE (50 mL). To this clear solution was then added acetic acid (0.86 g, 14.3 mmol, 3.1 equiv), followed by addition of powder NaBH(OAc)3 (CSN: 56553-60-7, mw=211.94): 2.9 g, 13.6 mmol, 3 equiv.) in one portion under N2 at r.t. The yellowish milky solution was stirred at r.t. overnight. LC/MS showed m/z 429.35/430.40 at t=2.123 min. TLC (5% of 7N NH3/MeOH in DCM) showed no SM. The reaction was diluted with DCM (40 mL) and quenched with 30 mL of conc. NH4OH in 70 mL of water. The two layers were separated, and the aqueous layer was extracted with DCM (10 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (15 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The product was purified on a 25 g-silica gel column (0-20%, 0-4 min; 20-40: 4-13 min; 40%: 13-25 min (A is % of 7N NH3/MeOH in DCM) to get 1.17 g (60%) of the title compound as an oil.

1. customat r.t
2. customat t=2.123 min
3. customquenched with 30 mL of conc. NH4OH in 70 mL of water
4. customThe two layers were separated
5. extractionthe aqueous layer was extracted with DCM (10 mL×2)
6. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (15 mL)
7. dry with materialdried (anhydrous potassium carbonate)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe product was purified on a 25 g-silica gel column (0-20%, 0-4 min
11. custom4-13 min