反应详情

温度

0 °C

The tert-butyl (2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-ylcarbamate (1.59 g, 4.97 mmol, 1.0 equiv) was dissolved in 15 mL of DMF and the solution cooled to 0° C. A solution of NaNTMS2 (1.0 M, 14.9 mmol, 3.0 equiv) was added via syringe at such a rate that the internal reaction temperature remains below 5° C. After stirring for 2 h LC/MS analysis showed formation of the cyclised product. Dimethylsulfate (940 mg, 0.71 mL, 7.5 mmol, 1.5 equiv) was added and the reaction mixture stirred overnight with concomitant warming to ambient temperature. LC/MS analysis showed formation of the desired methylated carbamate. The reaction was quenched by addition of 10% K2CO3 solution (˜30 mL) and the mixture stirred for 0.5 h. The volatile materials were removed in vacuo and the residue partitioned between EtOAc/water. The layers were separated and the organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The product was purified by flash chromatography on silica (40 g), eluting with 0-7% EtOAc in hexanes. This afforded 1.21 g (82% yield) of the desired tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(methyl)carbamate as a colorless liquid.

1. additionA solution of NaNTMS2 (1.0 M, 14.9 mmol, 3.0 equiv) was added via syringe at such a rate that the internal reaction temperature
2. customremains below 5° C
3. stirringthe reaction mixture stirred overnight
4. temperaturewith concomitant warming to ambient temperature
5. customThe reaction was quenched by addition of 10% K2CO3 solution (˜30 mL)
6. stirringthe mixture stirred for 0.5 h
7. customThe volatile materials were removed in vacuo
8. customthe residue partitioned between EtOAc/water
9. customThe layers were separated
10. washthe organic layer washed with brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. customevaporated
14. customThe product was purified by flash chromatography on silica (40 g)
15. washeluting with 0-7% EtOAc in hexanes