Ammonium Acetate → methyl 4-[(E)-1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-1-(4-fluorobenzoyl)-4-phenyl-3 butenyl]benzoate

HRID 1371017Notes

Reaction equation

HRID 1371017 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([CH:8]([C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=2)[CH2:9]/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:7])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Br[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]([P:47](=[O:58])([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])([F:46])[F:45])=[CH:40][CH:39]=1.C([O-])(=O)C.[NH4+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[C:54]([O:53][P:47]([C:44]([F:46])([F:45])[C:41]1[CH:42]=[CH:43][C:38]([CH2:37][C:8]([C:18]2[CH:19]=[CH:20][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:26][CH:27]=2)([C:6](=[O:7])[C:5]2[CH:28]=[CH:29][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:9]/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:39][CH:40]=1)([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:58])([CH3:55])([CH3:56])[CH3:57]

Participants

7

Reactant 4

HCID 517165Ammonium AcetateHCID 15922636Di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonateHCID 18510204methyl 4-[(E)-1-(4-fluorobenzoyl)-4-phenyl-3-butenyl]benzoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 86585140methyl 4-[(E)-1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-1-(4-fluorobenzoyl)-4-phenyl-3 butenyl]benzoate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of methyl 4-[(E)-1-(4-fluorobenzoyl)-4-phenyl-3-butenyl]benzoate (racemate) (0.430 g, 1.10 mmol), 18 crown 6 (0.236 g) and a catalytic amount of tetrabutylammonium iodide in THF (5 ml) degassed at −78° C. was added potassium tert-butoxide 1 M in THF (1.1 ml, 1.10 mmol). After a period of 0.5 h, a solution of di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonate (0.46 g, 1.11 mmol) in THF (5 ml) was added to the reaction mixture, and the reaction mixture was then stirred at room temperature for 1 hour. Saturated ammonium acetate solution (20 ml) was added and the mixture was extracted with ethyl acetate (20 ml). The organic phase was washed with brine and dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography using hexane/ethyl acetate 15% containing 1% triethylamine giving 0.39 g of the title compound.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 ml)
  2. washThe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by flash chromatography
  7. additioncontaining 1% triethylamine giving 0.39 g of the title compound

Sources & evidence

ORD record
ord-3261b524a3b347ea9edfab902c8d489d
Source dataset
uspto-grants-2003_06
Patent number
US06583126B2

Reaction notes

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