反应详情

(Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (90 mg, 0.20 mmol) is added to a solution of 2′-oxo-1′,2′-dihydro-3H-spiro[benzofuran-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (described in Intermediate 2) (48 mg, 0.17 mmol), (3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride (described in Intermediate 1, 54 mg, 0.17 mmol), and N,N-diisopropylethylamine (0.15 mL, 0.84 mmol) in DMF (3 mL), and the resulting mixture is stirred at ambient temperature for 3 h. The reaction mixture is then partitioned between saturated aqueous sodium bicarbonate solution (20 mL) and ethyl actetate (3×20 mL). The combined organic layers are washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue is purified by flash column chromatography on silica gel, eluting with a gradient of CH2Cl2:MeOH—100:0 to 90:10, to afford the title compound as a mixture of diastereomers.

1. customThe reaction mixture is then partitioned between saturated aqueous sodium bicarbonate solution (20 mL) and ethyl actetate (3×20 mL)
2. washThe combined organic layers are washed with brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated in vacuo
5. customThe residue is purified by flash column chromatography on silica gel
6. washeluting with a gradient of CH2Cl2