반응 #165861

ord-013d7b6537bc448c84a1e28f02e8d895

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도cooled to −20° to −15° C
  2. 2
    workup.ADDITIONThe reaction mixture was subsequently added to
  3. 3
    기타hydrogenated for 3 to 4 hours at about 25° C. (The buffer was prepared
  4. 4
    여과The catalyst was filtered after the completion of hydrogenation
  5. 5
    세척washed with water (100 mL)
  6. 6
    workup.ADDITIONThe filtrate was treated with activated charcoal and acetone (1.6 L)
  7. 7
    workup.ADDITIONwas added to the filtrate at 0° to 5° C
  8. 8
    workup.STIRRINGThe reaction mixture was stirred for 6 hours at 0° to 5° C.
  9. 9
    여과filtered

실험 절차

4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (Formula VIIIA; 20 g) was dissolved in N-methyl-2-pyrrolidone (100 mL) and cooled to −20° to −15° C. 4-Nitrobenzyl (2S,4S)-2-[(dimethylamino)carbonyl]-4-mercaptopyrrolidine-1-carboxylate (12 g) was added to the reaction mixture followed by the drop-wise addition of diisopropylethylamine (5.6 g) at −15° to −5° C. and the reaction mixture was stirred. The reaction mixture was subsequently added to a buffer containing 5% palladium-carbon (30 g) and hydrogenated for 3 to 4 hours at about 25° C. (The buffer was prepared using N-methylmorpholine (3.4 g) and appropriate quantity of hydrochloric acid so as to obtain a pH of 6.5 to 7.0 in distilled water (120 mL)). The catalyst was filtered after the completion of hydrogenation and washed with water (100 mL). The filtrate was treated with activated charcoal and acetone (1.6 L) was added to the filtrate at 0° to 5° C. The reaction mixture was stirred for 6 hours at 0° to 5° C. and filtered to obtain the title compound.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08841444B2uspto-grants-2014_09