Methanesulfonic Acid → (3R)-3-(2,6-Dichloro-4-hydroxy-benzyl)-1-(4,5,6,7-tetrahydro-1H-indazol-6-yl)-pyrrolidin-2-one

HRID 1013823Notes

Reaction equation

HRID 1013823 reaction equation
C([O:8][C:9]1[CH:30]=[C:29]([Cl:31])[C:12]([CH2:13][C@@H:14]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:27][C:26]4[NH:25][N:24]=[CH:23][C:22]=4[CH2:21][CH2:20]3)[C:15]2=[O:28])=[C:11]([Cl:32])[CH:10]=1)C1C=CC=CC=1.CS(O)(=O)=O>CSC>[Cl:32][C:11]1[CH:10]=[C:9]([OH:8])[CH:30]=[C:29]([Cl:31])[C:12]=1[CH2:13][C@@H:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:27][C:26]3[NH:25][N:24]=[CH:23][C:22]=3[CH2:21][CH2:20]2)[C:15]1=[O:28]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 67317121(3R)-3-(4-Benzyloxy-2,6-dichloro-benzyl)-1-(4,5,6,7-tetrahydro-1H-indazol-6-yl)-pyrrolidin-2-one

Product 1

HCID 67316410(3R)-3-(2,6-Dichloro-4-hydroxy-benzyl)-1-(4,5,6,7-tetrahydro-1H-indazol-6-yl)-pyrrolidin-2-oneYield 113.2%

Reagents, catalysts & solvents 1

HCID 1068Dimethyl SulfideSolvent

Procedure

To a solution of (3R)-3-(4-benzyloxy-2,6-dichloro-benzyl)-1-(4,5,6,7-tetrahydro-1H-indazol-6-yl)-pyrrolidin-2-one (3.93 g, 8.36 mmol) in dimethylsulfide (45 mL), add methane sulfonic acid (13.23 g, 138 mmol) and stir the mixture vigorously under nitrogen atmosphere at room temperature for 18 hours. Remove the solvent in vacuo and dilute the residue with water, adjust the pH to pH=7 with 5 N NaOH, and extract the mixture several times with ethyl acetate and THF. After drying the combined organic layer (Na2SO4), filter and concentrate under vacuum to afford 3.60 g (100%) of the title compound. MS (m/z): 381 (M+).

Workup

  1. customRemove the solvent in vacuo
  2. additiondilute the residue with water
  3. extractionextract the mixture several times with ethyl acetate and THF
  4. dry with materialAfter drying the combined organic layer (Na2SO4)
  5. filtrationfilter
  6. concentrationconcentrate under vacuum

Sources & evidence

ORD record
ord-189297764f9c4b8c93027942d8f3fb8c
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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