反应详情

Oxalyl chloride (0.58 ml, 6.7 mmol) and DMF (few drops) were added to a solution of (R)-2-{[4-(5-chloropyridin-2-yloxy)piperidine-1sulfonyl)amino}-3-methylbutyric acid (1.05 g, 2.7 mmol), [prepared as described in Step 1 above], in methylene chloride (85 ml) and the reaction mixture was stirred overnight at RT. After removal of the organics, the residue was redissolved in methylene chloride (40 ml) and N,O-bis-trimethylsilylhydroxylamine (1.7 g, 9.4 mmol) was added. After 3 h, the reaction was concentrated, methanol (20 ml) was added and after stirring for an additional 30 min., the solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine, dried over MgSO4, and concentrated. Chromatography (SiO2, 1-2% methanol/methylene chloride) gave N-hydroxy-2-(R)-{[4-(5-chloropyridin-2-yl-oxy)piperidine-1-sulfonyl]amino}-3-methylbutyramide as a white solid (35%), mp 97.0-98.4° C.

1. customAfter removal of the organics, the residue
2. dissolutionwas redissolved in methylene chloride (40 ml)
3. waitAfter 3 h
4. concentrationthe reaction was concentrated
5. additionmethanol (20 ml) was added
6. stirringafter stirring for an additional 30 min.
7. customthe solvent was removed in vacuo
8. dissolutionThe residue was dissolved in ethyl acetate
9. washwashed with water and brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated