تفاعل #2022016

ord-85d20ed9b1b34d57a250c4c1a80fb5f2

معادلة التفاعل

O=C(O)[C@H]1C[C@@H](O)CN1C(=O)Nc1cc(NS(=O)(=O)CCl)c(Cl)cc1F
(2R-cis)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]4-hydroxy-2-pyrrolidinecarboxylic acid
O=S(=O)(O)O
sulfuric acid
→
O=C1[C@H]2C[C@@H](O)CN2C(=O)N1c1cc(NS(=O)(=O)CCl)c(Cl)cc1F
title compound
المردود 88.9%
O=C1[C@H]2C[C@@H](O)CN2C(=O)N1c1cc(NS(=O)(=O)CCl)c(Cl)cc1F
(6R-trans)-1-chloro-N-[2-chloro-4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamide
المردود 88.9%

المتفاعلات

O=C(O)[C@H]1C[C@@H](O)CN1C(=O)Nc1cc(NS(=O)(=O)CCl)c(Cl)cc1F
(2R-cis)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]4-hydroxy-2-pyrrolidinecarboxylic acid
O=S(=O)(O)O
sulfuric acid

الكواشف

لا شيء

المذيبات

CC(=O)CC(C)C
methyl isobutyl ketone

ظروف التفاعل

درجة الحرارة
0°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةthe clear solution was heated to reflux
  2. 2
    أخرىAt 90° C.
  3. 3
    درجة الحرارةat reflux the suspension
  4. 4
    workup.STIRRINGto stir for 1 hour at this temperature
  5. 5
    ترشيحAfter filtration
  6. 6
    أخرىdrying at 60° C.

الإجراء التجريبي

295.5 g (0.25 mol) of (2R-cis)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]4-hydroxy-2-pyrrolidinecarboxylic acid was suspended in 150 g of methyl isobutyl ketone at room temperature. 12.75 g (0.125 mol) of concentrated sulfuric acid was added and the clear solution was heated to reflux. At 90° C. a precipitate appeared. After an additional 20 minutes of stirring at reflux the suspension was cooled to 0° C. and allowed to stir for 1 hour at this temperature. After filtration and drying at 60° C., 91.65 g (86.6%) of the title compound was obtained as beige crystals melting at 198-200° C. (purity: 97%).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US06384234B1uspto-grants-2002_05