Iodine → HCID 89522300, compound

HRID 529732Notes

Reaction equation

HRID 529732 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]3[C@H:19]([C:22]4[C:27]([Br:28])=[CH:26][CH:25]=[C:24]([N:29]([CH3:31])[CH3:30])[N:23]=4)[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[I:34]I>CO.S([O-])([O-])(=O)=O.[Ag+2]>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]3[C@H:19]([C:22]4[C:27]([Br:28])=[CH:26][C:25]([I:34])=[C:24]([N:29]([CH3:30])[CH3:31])[N:23]=4)[CH2:20][CH2:21][C@@H:14]23)[CH:4]=[C:3]([C:2]([F:1])([F:32])[F:33])[CH:8]=1

Participants

5

Reactant 2

HCID 807IodineHCID 89522484HCID 89522484, compound

Product 1

HCID 89522300HCID 89522300, compoundYield 72.8%

Reagents, catalysts & solvents 2

HCID 178418844HCID 178418844, compoundCatalystHCID 887MethanolSolvent

Procedure

To a slurry of (1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-5-[3-bromo-6-(dimethylamino)pyridin-2-yl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one (200 mg, 0.372 mmol) in MeOH (7.25 mL) under nitrogen at room temperature was added silver sulfate (116 mg, 0.372 mmol), followed by iodine (94 mg, 0.372 mmol). The resulting mixture was stirred for 1 hour. The reaction was partitioned with ethyl acetate and aqueous sodium hydroxide (1.0 M). The organic was then washed with aqueous saturated sodium thiosulfate and the combined aqueous layers were extracted with ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to yield (1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-5-[3-bromo-6-(dimethylamino)-5-iodopyridin-2-yl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one (180 mg, 0.271 mmol). MS ESI calc'd. for C21H18BrF6N3O2 [M+H]+ 666.0, found 666.1.

Workup

  1. customThe reaction was partitioned with ethyl acetate and aqueous sodium hydroxide (1.0 M)
  2. washThe organic was then washed with aqueous saturated sodium thiosulfate
  3. extractionthe combined aqueous layers were extracted with ethyl acetate
  4. washThe combined organics were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-e3ee30ebcbfb4687a3d562705e971574
Source dataset
uspto-grants-2016_05
Patent number
US09346825B2

Reaction notes

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