Iodine → HCID 89522300, compound

HRID 540473Notes

Reaction equation

HRID 540473 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-e8095f803b62471d8d4b2ff005447802
Source dataset
uspto-grants-2014_10
Patent number
US08871738B2

Reaction notes

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