Sulfuric Acid → (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

HRID 432952

Reaction equation

HRID 432952 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH2:12][Cl:13])(=[O:11])=[O:10])=[CH:6][C:5]([NH:14][C:15]([N:17]2[CH2:21][C@H:20]([OH:22])[CH2:19][C@@H:18]2[C:23](O)=[O:24])=[O:16])=[C:4]([F:26])[CH:3]=1.S(=O)(=O)(O)O>C(C(C)=O)C(C)C>[Cl:13][CH2:12][S:9]([NH:8][C:7]1[CH:6]=[C:5]([N:14]2[C:23](=[O:24])[C@H:18]3[CH2:19][C@@H:20]([OH:22])[CH2:21][N:17]3[C:15]2=[O:16])[C:4]([F:26])=[CH:3][C:2]=1[Cl:1])(=[O:11])=[O:10]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 53809153(2R-cis)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]4-hydroxy-2-pyrrolidinecarboxylic acid

Product 1

HCID 10982513(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]methanesulfonamideYield 88.9%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Conditions

Temperature
0 °C

Procedure

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%).

Workup

  1. temperaturethe clear solution was heated to reflux
  2. customAt 90° C.
  3. temperatureat reflux the suspension
  4. stirringto stir for 1 hour at this temperature
  5. filtrationAfter filtration
  6. customdrying at 60° C.

Sources & evidence

ORD record
ord-5326204c9d474a91bb878307a3b51a55
Source dataset
uspto-grants-2003_12
Patent number
US06664400B2

Linked notes

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