反应详情

To a solution of tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate (Intermediate 187, 1.27 g) in methylene chloride (15 mL) at 0° C. were added diisopropylethylamine (1.2 mL) and methanesulfonyl chloride (0.50 mL). At the same time in a separate flask, to a solution of 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonitrile (Intermediate 60) (0.66 g) in DMF (8 mL) at 0° C. was added 60% suspension in oil of NaH (0.25 g). After 30 minutes, the mesylate solution was diluted with methylene chloride, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated. This residue was dissolved in DMF (5 mL) and added to the sodium salt of Intermediate 60. The reaction was stirred over the weekend, diluted with ethyl acetate, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated to give the product.

1. washwashed with NaHCO3 and brine
2. dry with materialdried over sodium sulfate
3. concentrationconcentrated
4. dissolutionThis residue was dissolved in DMF (5 mL)
5. additionadded to the sodium salt of Intermediate 60
6. additiondiluted with ethyl acetate
7. washwashed with NaHCO3 and brine
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated
10. customto give the product