[(4-Fluoro-3-phenoxyphenyl)methyl](triphenyl)phosphanium bromide → 1-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1,3-butadiene

HRID 1596824Notes

Reaction equation

HRID 1596824 reaction equation
[Br-].[F:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:5][C:4]=1[O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([Li])CCC.[F:41][C:42](=[C:45]([CH:53]1[CH2:55][CH2:54]1)[C:46]1[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=1)[CH:43]=O>O1CCCC1>[Cl:52][C:49]1[CH:48]=[CH:47][C:46]([C:45]([CH:53]2[CH2:55][CH2:54]2)=[C:42]([F:41])[CH:43]=[CH:7][C:6]2[CH:27]=[CH:28][C:3]([F:2])=[C:4]([O:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:5]=2)=[CH:51][CH:50]=1

Participants

5

Reactant 3

HCID 21703142[(4-Fluoro-3-phenoxyphenyl)methyl](triphenyl)phosphanium bromideHCID 540115002-Fluoro-3-cyclopropyl-3-(p-chlorophenyl)acrylaldehydeHCID 178418339Butyllithium

Product 1

HCID 540353111-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1,3-butadieneYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-2.5 °C

Procedure

A mixture of (4-fluoro-3-phenoxybenzyl)triphenyl phosphonium bromide (41.77 g, 0.077 mol) in tetrahydrofuran is cooled to 55 to −60° C., treated dropwise with a 2.5 M solution of butyllithium in hexanes (32.15 mL, 0.080 mol), warmed to and stirred at room temperature for 2 hours, cooled 55 to −60° C., treated dropwise with a solution of 2-fluoro-3-cyclopropyl-3-(p-chlorophenyl)acrylaldehyde (15.7 g, 0.070 mol) in tetrahydrofuran, warmed to and stirred at room temperature overnight, and quenched with ethyl acetate and 2 N hydrochloric acid. The resultant aqueous mixture is extracted with ethyl acetate. The organic extracts are combined, washed sequentially with water, 2 N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a residue. Flash column chromatography of the residue using silica gel and an ethyl acetate/hexanes solution (1:9) gives the title product as an oil (26.0 g, 91%).

Workup

  1. temperaturewarmed to and
  2. temperaturecooled 55 to −60° C.
  3. temperaturewarmed to and
  4. stirringstirred at room temperature overnight
  5. customquenched with ethyl acetate and 2 N hydrochloric acid
  6. extractionThe resultant aqueous mixture is extracted with ethyl acetate
  7. washwashed sequentially with water, 2 N hydrochloric acid and water
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto obtain a residue

Sources & evidence

ORD record
ord-94e1c84d5dcb49a299479df6ad5199f7
Source dataset
uspto-grants-2001_09
Patent number
US06291721B1

Reaction notes

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