反应详情

温度

-78 °C

To a solution of diethylaminosulfur trifluoride (DAST, 0.65 mL) in dry methylene chloride (49 mL) at -78° C. under N2 is added a solution of 4-hydroxy-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester (EXAMPLE 74, Step 1, 2.25 g) in dry methylene chloride (47 mL) over 2 mins. The resulting mixture is stirred at -78° C. for 1 hr and at ambient temperature for 30 mins and is then adjusted to pH 8 with saturated aqueous sodium bicarbonate (50 mL), diluted with water (50 mL), and the layers are separated. The organic phase is washed with water (25 mL) and saline (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is chromatographed on silica gel (230-400 mesh, 150 g), eluting with methanol/methylene chloride (0.5/99.5). Those fractions with an Rf =0.27 by TLC (ethyl acetate/hexane, 25/75) are pooled and concentrated to give the title compound (contaminated with approx. 15% of the elimination side product). An analytical sample is prepared by radial chromatography (1000μ silica gel rotor, ethyl acetate/hexane (20/80) eluent), mp 116-118° C.

1. customthe layers are separated
2. washThe organic phase is washed with water (25 mL) and saline (25 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customthe residue is chromatographed on silica gel (230-400 mesh, 150 g)
6. washeluting with methanol/methylene chloride (0.5/99.5)
7. concentrationconcentrated