Potassium Iodide → (S)-3-(2-amino-2'-bromo-5'-fluoro-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)-2,2-dimethylpropanenitrile

HRID 335833Notes

Reaction equation

HRID 335833 reaction equation
[I-].[K+].FC(F)(F)S([O:8][CH2:9][C:10]([C:13]#[N:14])([CH3:12])[CH3:11])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:23][C:24]1[O:25][CH2:26][C@@:27]2([N:44]=1)[C:40]1[CH:39]=[C:38](O)[CH:37]=[C:36]([F:42])[C:35]=1[O:34][C:33]1[C:28]2=[CH:29][C:30]([Br:43])=[CH:31][CH:32]=1>CN(C=O)C>[NH2:23][C:24]1[O:25][CH2:26][C@:27]2([N:44]=1)[C:28]1[CH:29]=[C:30]([Br:43])[CH:31]=[CH:32][C:33]=1[O:34][C:35]1[C:40]2=[CH:39][C:38]([O:8][CH2:9][C:10]([CH3:11])([CH3:12])[C:13]#[N:14])=[CH:37][C:36]=1[F:42]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 58466133(S)-2-amino-7'-bromo-4'-fluoro-5H-spiro[oxazole-4,9'-xanthen]-2'-olHCID 866407352-Cyano-2-methylpropyl trifluoromethanesulfonate

Product 1

HCID 67383700(S)-3-(2-amino-2'-bromo-5'-fluoro-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)-2,2-dimethylpropanenitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a flask charged with potassium iodide (273 mg, 1.643 mmol), 2-cyano-2-methylpropyl trifluoromethanesulfonate (1140 mg, 4.93 mmol), cesium carbonate (3212 mg, 9.86 mmol), and (S)-2-amino-7′-bromo-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (1200 mg, 3.29 mmol) was added 10 ml of DMF. The resulting slurry was heated for 1 hour at 60° C. The solution was quenched with water (20 mL). The aqueous layer was extracted with CH2Cl2 (3×25 mL) and the combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After being filtered and concentrated, the derived residue was purified via silica gel column chromatography using 15-70% 90/10/1 (CH2Cl2/MeOH/ammonia) in CH2Cl2 to afford (S)-3-(2-amino-2′-bromo-5′-fluoro-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)-2,2-dimethylpropanenitrile as a brown solid. MS m/z=446.0 [M+H].

Workup

  1. customThe solution was quenched with water (20 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×25 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter being filtered
  6. concentrationconcentrated
  7. customthe derived residue was purified via silica gel column chromatography

Sources & evidence

ORD record
ord-237cceb3af404ed8a108d38d7a88be64
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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