[4-(Methoxycarbonyl)benzyl](triphenyl)phosphonium bromide → 4-{(E)-3-cyclohexyl-3-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-propenyl}-benzoic acid methyl ester

HRID 417169

Reaction equation

HRID 417169 reaction equation
[Br-].[C:2]([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:4][CH3:5])=[O:3].CC(C)([O-])C.[K+].[CH:38]1([CH:44]([N:47]2[C:51]3[CH:52]=[C:53]([F:57])[C:54]([F:56])=[CH:55][C:50]=3[N:49]=[C:48]2[C:58]2[C:59]([O:66][CH3:67])=[N:60][C:61]([O:64][CH3:65])=[CH:62][CH:63]=2)[CH:45]=O)[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>O1CCCC1>[CH3:5][O:4][C:2](=[O:3])[C:6]1[CH:7]=[CH:8][C:9](/[CH:10]=[CH:45]/[CH:44]([CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[N:47]2[C:51]3[CH:52]=[C:53]([F:57])[C:54]([F:56])=[CH:55][C:50]=3[N:49]=[C:48]2[C:58]2[C:59]([O:66][CH3:67])=[N:60][C:61]([O:64][CH3:65])=[CH:62][CH:63]=2)=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 2764257[4-(Methoxycarbonyl)benzyl](triphenyl)phosphonium bromideHCID 23665647Potassium tert-butoxideHCID 86639905Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetaldehyde

Product 1

HCID 666194594-{(E)-3-cyclohexyl-3-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-propenyl}-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 296 mg (0.60 mmol) 4-carbomethoxybenzyl triphenylphosphonium bromide in 5 ml tetrahydrofuran was added 68 mg (0.602 mmol) potassium tert-butoxide at 0° C. and the reaction mixture was stirred for 15 min. Then, 250 mg (0.60 mmol) cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetaldehyde was added at 0° C. The cooling bath was removed and the reaction mixture was stirred for 4 hours at room temperature. The reaction was poured on 30 ml 10% aqueous citric acid and 30 ml ethyl acetate and the layers were separated. The aqueous layer was extracted a second time with 30 ml ethyl acetate. The combined organic layers were washed with 30 ml brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30). Colorless solid (67%). MS (TurboSpray): m/z=547.2 [M+H].

Workup

  1. customThe cooling bath was removed
  2. stirringthe reaction mixture was stirred for 4 hours at room temperature
  3. additionThe reaction was poured on 30 ml 10% aqueous citric acid and 30 ml ethyl acetate
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted a second time with 30 ml ethyl acetate
  6. washThe combined organic layers were washed with 30 ml brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by silica chromatography
  11. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30)

Sources & evidence

ORD record
ord-0af6e13729f446a0b8d5a316f8b8fcf8
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Linked notes

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