Potassium Iodide → Ethyl 3-[4-({4'-[3-(diethoxyphosphoryl)propoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2-fluorophenyl]propanoate

HRID 273423Notes

Reaction equation

HRID 273423 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:11]=[C:12]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([OH:23])=[CH:18][C:17]=3[CH3:24])[CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:4][C:3]=1[CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].[H-].[Na+].Br[CH2:35][CH2:36][CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41].[I-].[K+]>CN(C)C=O>[CH2:43]([O:42][P:38]([CH2:37][CH2:36][CH2:35][O:23][C:19]1[CH:18]=[C:17]([CH3:24])[C:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][O:8][C:6]3[CH:5]=[CH:4][C:3]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:2]([F:1])[CH:7]=3)[CH:11]=2)=[C:21]([CH3:22])[CH:20]=1)([O:39][CH2:40][CH3:41])=[O:45])[CH3:44]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 283500Diethyl (3-bromopropyl)phosphonateHCID 58903128Ethyl 3-{2-fluoro-4-[(4'-hydroxy-2',6'-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate

Product 1

HCID 58903140Ethyl 3-[4-({4'-[3-(diethoxyphosphoryl)propoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2-fluorophenyl]propanoateYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-{2-fluoro-4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (315 mg, 0.74 mmol) in N,N-dimethylformamide (4 mL) was added sodium hydride (60%, 31 mg, 0.78 mmol) at 0° C. with stirring, and the mixture was stirred at room temperature for 30 min. Diethyl (3-bromopropyl)phosphonate (578 mg, 2.23 mmol) and potassium iodide (37 mg, 0.22 mmol) were added, and the mixture was further stirred overnight at 60° C. The reaction mixture was concentrated under reduced pressure. Brine was added to the residue, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-1/4) and then by preparative HPLC (gradient cycle A) to give the title compound (0.22 g, yield 50%) as a colorless oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. stirringthe mixture was further stirred overnight at 60° C
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionBrine was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate
  6. dry with materialThe extract was dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-1/4)

Sources & evidence

ORD record
ord-582230eb2771405f890fe0a74b8a7d7a
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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