18-Crown-6 → Methyl 4-[1-{4-[2-(tert-butoxy)-1,1-difluoro-2-oxoethoxy]benzyl}-1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoate

HRID 1371019Notes

Reaction equation

HRID 1371019 reaction equation
[C:1]([O:5][C:6](=[O:38])[C:7]([F:37])([F:36])[O:8][C:9]1[CH:35]=[CH:34][C:12]([CH2:13][CH:14]([C:24]2[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=2)[C:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[O:16])=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].Br[CH2:64][C:65]1[CH:70]=[CH:69][C:68]([C:71]([P:74](=[O:85])([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])[O:75][C:76]([CH3:79])([CH3:78])[CH3:77])([F:73])[F:72])=[CH:67][CH:66]=1>C1COCC1>[C:1]([O:5][C:6](=[O:38])[C:7]([F:36])([F:37])[O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][C:14]([C:24]2[CH:25]=[CH:26][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=2)([CH2:64][C:65]2[CH:70]=[CH:69][C:68]([C:71]([P:74]([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])([O:75][C:76]([CH3:77])([CH3:79])[CH3:78])=[O:85])([F:72])[F:73])=[CH:67][CH:66]=2)[C:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[O:16])=[CH:34][CH:35]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 15922636Di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonateHCID 18510241Methyl 4-[1-{4-[2-(tert-butoxy)-1,1-difluoro-2-oxoethoxy]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 18510258Methyl 4-[1-{4-[2-(tert-butoxy)-1,1-difluoro-2-oxoethoxy]benzyl}-1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoateYield 48.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-[1-{4-[2-(tert-butoxy)-1,1-difluoro-2-oxoethoxy]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoate (0.176 g, 0.333 mmol)) in degassed THF (1.7 ml), were added at −20° C. 18-crown-6 (0.15 g) and potassium tert-butoxide 1 M in THE (0.379 ml ). Di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonate (0.156 g, 0.378 mmol) was then added and the reaction mixture was allowed to warm to room temperature. The reaction was quenched with saturated ammonium acetate solution and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography using hexane/ethyl acetate 20% giving 0.140 g of the title compound.

Workup

  1. customThe reaction was quenched with saturated ammonium acetate solution
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a3c05e608267479fad71a001cb8aa16a
Source dataset
uspto-grants-2003_06
Patent number
US06583126B2

Reaction notes

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