反应详情

温度

50 °C

To a solution of 3.96 g (3R,4R,5S)-4-azido-5-tert.-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethylester (10 mmol) in 50 ml ethyl acetate were added 2.0 g wet Raney-Cobalt catalyst and the suspension was stirred and hydrogenated at room temperature for 20 h (˜1.1 bar H2; 500 rpm). After removing the catalyst by filtration, 1.53 ml triethylamine (11 mmol =1.11 g) and 0.99 ml acetic anhydride (10.5 mmol =1.07 g) were added all at once and the colorless solution was stirred at room temperature for 1 h. Then 5.26 ml 5.7 M HBr/acetic acid (30 mmol HBr) were added to the colorless solution and the reaction mixture was stirred at room temperature for 20 h. Then ca. 55 ml 2 N NaOH (pH ca. 9.5) were added under stirring and the organic layer was separated and washed twice with 30 ml, a total of 60 ml 20% brine. All three aqueous layers were extracted sequentially and twice with 30 ml, a total of 60 ml ethyl acetate and the combined organic layers were dried (Na2SO4). After filtration and removal of the solvent by rotary evaporation (50°/≧1 mbar) the yellowish, viscous residue (3.47 g) was dissolved in 20 ml ethanol and added under stirring to a 50° C. warm solution of 0.98 g ortho-phosphoric acid (10 mmol) in 40 ml ethanol over 30 min (after the addition of two third, the 50° C. warm solution was seeded with pure title product). The white suspension was cooled down (2 h) and stirred at 0° C. for 3 h. The crystals were filtered, washed with ca. 20 ml acetone and dried (50°/10 mbar/16 h) affording 3.41 g (83.2%) white, crystalline phosphoric acid salt, m.p. 198-199° C. (dec.).

1. customAfter removing the catalyst
2. additionwere added all at once and the colorless solution
3. stirringwas stirred at room temperature for 1 h
4. stirringthe reaction mixture was stirred at room temperature for 20 h
5. stirringunder stirring
6. customthe organic layer was separated
7. washwashed twice with 30 ml
8. extractionAll three aqueous layers were extracted sequentially and twice with 30 ml
9. dry with materiala total of 60 ml ethyl acetate and the combined organic layers were dried (Na2SO4)
10. filtrationAfter filtration and removal of the solvent
11. customby rotary evaporation (50°/≧1 mbar) the yellowish, viscous residue (3.47 g)
12. dissolutionwas dissolved in 20 ml ethanol
13. additionadded
14. stirringunder stirring to a 50° C.
15. additionafter the addition of two third