4-Toluenesulfonyl chloride → 1-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1,3-butadiene

HRID 1596826Notes

Reaction equation

HRID 1596826 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH:30]2[CH2:32][CH2:31]2)=[C:11]([F:29])[CH:12](O)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:15]=2)=[CH:6][CH:5]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1>O1CCCC1>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH:30]2[CH2:32][CH2:31]2)=[C:11]([F:29])[CH:12]=[CH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:15]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 541714401-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1-buten-3-ol

Product 1

HCID 540353111-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1,3-butadieneYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

A suspension of sodium hydride (6.3 mg, 0.26 mmol) in tetrahydrofuran (1 mL) is treated with a solution of 1-(p-chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1-buten-3-ol (106.7 mg, 0.25 mmol) in tetrahydrofuran (1.5 mL), stirred at 50° C. for 10 minutes, cooled to room temperature, treated with a solution of p-toluenesulfonyl chloride (49.6 mg, 0.26 mmol) in tetrahydrofuran (1 mL), stirred at 60° C. for 1 hour, quenched with water, and extracted with ethyl acetate. The combined organic extracts are washed sequentially with water, saturated sodium hydrogen carbonate solution and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a residue. Flash chromatography of the residue using silica gel and a 1:9 ethyl acetate/hexanes solution gives the title product (62 mg, 61% yield) which is identified by NMR spectral analyses.

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred at 60° C. for 1 hour
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts are washed sequentially with water, saturated sodium hydrogen carbonate solution and water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto obtain a residue

Sources & evidence

ORD record
ord-272643f2317740ea9c4206bb86cf16bd
Source dataset
uspto-grants-2001_09
Patent number
US06291721B1

Reaction notes

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