Iodine → (2S,3S)-3-(3-fluorophenyl)-3-(3-iodo-1H-indol-1-yl)propane-1,2-diol

HRID 2110367Notes

Reaction equation

HRID 2110367 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14]2)[C@H:9]([OH:12])[CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1.[OH-].[K+].[I:24]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([I:24])=[CH:14]2)[C@H:9]([OH:12])[CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 807IodineHCID 14797Potassium HydroxideHCID 24477Sodium ThiosulfateHCID 68903774(2S,3S)-3-(3-fluorophenyl)-3-(1H-indol-1-yl)propane-1,2-diol

Product 1

HCID 68906971(2S,3S)-3-(3-fluorophenyl)-3-(3-iodo-1H-indol-1-yl)propane-1,2-diolYield 48.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,3S)-3-indol-1-yl-3-(3-fluorophenyl)-propane-1,2-diol (EXAMPLE 47, Step 5, 1.34 g, 4.56 mmol) in N,N-dimethylformamide (20 mL) was added pulverized solid potassium hydroxide (0.76 g, 13.68 mmol). The mixture was stirred for 15 minutes under nitrogen at room temperature, whereupon iodine (1.21 g, 4.72 mmol) was added in one portion. The mixture was stirred for 30 minutes at room temperature, then poured into 100 mL of a 5% aqueous sodium thiosulfate solution. The solution was extracted 3 times with ethyl acetate and the combined extracts were washed 3 times with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Biotage chromatography (FlasH40i, silica, 40% ethyl acetate/hexane) to yield 0.91 g (48%) of (2S,3S)-3-(3-fluorophenyl)-3-(3-iodo-1H-indol-1-yl)propane-1,2-diol as a dark brown oil. MS (ES) m/z 411.9.

Workup

  1. additionwas added in one portion
  2. extractionThe solution was extracted 3 times with ethyl acetate
  3. washthe combined extracts were washed 3 times with water
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified via Biotage chromatography (FlasH40i, silica, 40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f152b0f6011d44b4bca71e4d68aecf59
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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