Hydrochloric Acid → HCID 54373278, compound

Temperature

120 °C

32.07 g (87.8 mmole) of 4-t-butyldimethylsilyloxy-(2R)-(3,4-dichlorophenyl)butane-1,2-diol [prepared as described in step (c) above] and 1.07 g (8.76 mmole) of 4-dimethylaminopyridine were dissolved in 320 ml of pyridine, and 10.19 ml (0.132 mole) of methanesulfonyl chloride was slowly added dropwise, whilst ice-cooling. The mixture was then stirred under a nitrogen atmosphere at the same temperature for 2 hours. The reaction mixture was then poured into 1500 ml of ice-cooled 10% w/v aqueous hydrochloric acid and then extracted three times, each time with 200 ml of ethyl acetate. The combined organic extracts were washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was dried under reduced pressure. The residue was then dissolved in 300 ml of anhydrous dimethylformamide, and 11.41 g (0.18 mole) of sodium azide were added. The mixture was then heated under a nitrogen atmosphere at 120° C. for 4 hours. At the end of this time, the reaction mixture was cooled to room temperature, poured into 1000 ml of a saturated aqueous solution of sodium chloride and then extracted three times, each time with 500 ml of ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel flash column chromatography, using a gradient elution method, with mixtures of hexane and ethyl acetate ranging from 10:1 to 5:1 by volume as the eluent, to obtain 29.3 g (yield 85%) of the title compound as a colorless oil.

1. temperaturecooling
2. temperaturecooled 10%
3. extractionextracted three times
4. washThe combined organic extracts were washed with a saturated aqueous solution of sodium chloride
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was removed by distillation under reduced pressure
7. customthe resulting residue was dried under reduced pressure
8. dissolutionThe residue was then dissolved in 300 ml of anhydrous dimethylformamide
9. temperatureAt the end of this time, the reaction mixture was cooled to room temperature
10. extractionextracted three times
11. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
12. customthe solvent was removed by distillation under reduced pressure
13. customThe resulting residue was purified by silica gel flash column chromatography
14. washa gradient elution method

ORD record

ord-e7336dc6ec3d46508c7ce95db01b2ad2

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06448247B1