Potassium Phosphate, Tribasic → (2S,3S)-3-(3-fluorophenyl)-3-{3-[2-fluorophenyl]-1H-indol-1-yl}propane-1,2-diol

HRID 2110368Notes

Reaction equation

HRID 2110368 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)[C:15](I)=[CH:14]2)[C@H:9]([OH:12])[CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1.[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[F:23])=[CH:14]2)[C@H:9]([OH:12])[CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343542-Fluorophenylboronic acidHCID 68906971(2S,3S)-3-(3-fluorophenyl)-3-(3-iodo-1H-indol-1-yl)propane-1,2-diol

Product 1

HCID 68906651(2S,3S)-3-(3-fluorophenyl)-3-{3-[2-fluorophenyl]-1H-indol-1-yl}propane-1,2-diolYield 60.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (2S,3S)-3-(3-fluorophenyl)-3-(3-iodo-1H-indol-1-yl)propane-1,2-diol (0.25 g, 0.61 mmol), 2-fluorobenzeneboronic acid (0.12 g, 0.85 mmol), and potassium phosphate (0.39 g, 1.83 mmol) in N,N-dimethylformamide (10 mL) was degassed with nitrogen for 5 minutes then a catalytic amount (0.02 g) of [1,4-bis-(diphenylphosphine)butane]palladium (II) dichloride was added. The solution was heated to 90° C. for 3 hours then cooled and poured into 100 mL of water. The aqueous mixture was extracted 3 times with ethyl acetate and the combined extracts were then washed 2 times with water. The ethyl acetate was dried by filtration through a plug of silica gel then concentrated. The residue was purified by Biotage chromatography (FlasH40i, silica, 40% ethyl acetate/hexane) to yield 0.14 g of (2S,3S)-3-(3-fluorophenyl)-3-{3-[2-fluorophenyl]-1H-indol-1-yl}propane-1,2-diol as an oil, which was used in the next step without further purification.

Workup

  1. customwas degassed with nitrogen for 5 minutes
  2. additiona catalytic amount (0.02 g) of [1,4-bis-(diphenylphosphine)butane]palladium (II) dichloride was added
  3. temperaturethen cooled
  4. additionpoured into 100 mL of water
  5. extractionThe aqueous mixture was extracted 3 times with ethyl acetate
  6. washthe combined extracts were then washed 2 times with water
  7. dry with materialThe ethyl acetate was dried by filtration through a plug of silica gel
  8. concentrationthen concentrated
  9. customThe residue was purified by Biotage chromatography (FlasH40i, silica, 40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e9c4c8c4b6514586b892a7b83abceb43
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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