1253-47-0 → trans 4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid methyl ester

HRID 1669307Notes

Reaction equation

HRID 1669307 reaction equation
[Cl-].[CH3:2][O:3][C:4]([C:6]1[CH:31]=[CH:30][C:9]([CH2:10][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:8][CH:7]=1)=[O:5].CC(C)([O-])C.[K+].[F:38][C:39]([F:62])([F:61])[CH2:40][CH2:41][CH:42]([C:45]1[CH:46]=[N:47][C:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:53][CH:52]=2)=[CH:49][CH:50]=1)[CH:43]=O>C1(C)C=CC=CC=1>[CH3:2][O:3][C:4](=[O:5])[C:6]1[CH:7]=[CH:8][C:9](/[CH:10]=[CH:43]/[CH:42]([C:45]2[CH:46]=[N:47][C:48]([C:51]3[CH:56]=[CH:55][C:54]([C:57]([F:60])([F:58])[F:59])=[CH:53][CH:52]=3)=[CH:49][CH:50]=2)[CH2:41][CH2:40][C:39]([F:38])([F:62])[F:61])=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 180010581253-47-0HCID 23665647Potassium tert-butoxideHCID 866203575,5,5-Trifluoro-2-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-pentanal

Product 1

HCID 86620358trans 4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid methyl esterYield 41%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

(4-Methoxycarbonyl-benzyl)-triphenyl-phosphonium chloride (6.7 g, 15 mmol) is suspended in anhydrous toluene (25 mL) and potassium tert-butoxide (1.7 g, 15 mmol) is added at room temperature in one portion. The mixture is allowed to stir under nitrogen for 1 h. Meanwhile, 5,5,5-trifluoro-2-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-pentanal (3.61 g, 10.0 mmol) is dissolved in another portion of the toluene (25 mL), and kept at room temperature. The mixture is then cooled to 0° C. with ice water, and then the ketone is transferred by cannula. The reaction is allowed to stir at 0° C. for 10 min, then the ice bath is removed. The reaction is allowed to warm to room temperature and monitored by HPLC. Upon complete conversion, the reaction is carefully quenched with saturated ammonium chloride solution, and diluted with ethyl acetate, then extracted. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, then filtered and concentrated. The cis and trans 4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid methyl ester (2.0 g, 4.1 mmol) are isolated as pure regioisomers (1:1) after column chromatography, 31% total yield.

Workup

  1. customkept at room temperature
  2. stirringto stir at 0° C. for 10 min
  3. customthe ice bath is removed
  4. customUpon complete conversion, the reaction is carefully quenched with saturated ammonium chloride solution
  5. additiondiluted with ethyl acetate
  6. extractionextracted
  7. washThe organic layer is washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-bc7de05ad3444c1f8f6c291a3998a4c8
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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