Tert-butyl 2-[4-(bromomethyl)phenoxy]-2,2-difluoroacetate → Methyl 4-[1-{4-[2-(tert-butoxy)-1,1-difluoro-2-oxoethoxy]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoate

HRID 1371018Notes

Reaction equation

HRID 1371018 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[O:12])=[CH:6][CH:5]=1.CC(C)([O-])C.[K+].Br[CH2:28][C:29]1[CH:45]=[CH:44][C:32]([O:33][C:34]([F:43])([F:42])[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:31][CH:30]=1>C1COCC1>[C:38]([O:37][C:35](=[O:36])[C:34]([F:43])([F:42])[O:33][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][CH:10]([C:7]2[CH:6]=[CH:5][C:4]([C:3]([O:2][CH3:1])=[O:20])=[CH:9][CH:8]=2)[C:11]([C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)=[O:12])=[CH:45][CH:44]=1)([CH3:41])([CH3:39])[CH3:40]

Participants

5

Reactant 3

HCID 15391315Tert-butyl 2-[4-(bromomethyl)phenoxy]-2,2-difluoroacetateHCID 18510220Methyl 4-[2-(4-fluorophenyl)-2-oxoethyl]benzoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 18510241Methyl 4-[1-{4-[2-(tert-butoxy)-1,1-difluoro-2-oxoethoxy]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoateYield 60.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl-4-[2-(4-fluorophenyl)-2-oxoethyl]benzoate (0.150 g, 0.551 mmol) (Example 1, Step 2) in degassed THF at −20° C. was added potassium tert-butoxide (0.606 ml), followed by a solution of tert-butyl 2-[4-(bromomethyl)phenoxy]-2,2-difluoroacetate (H. Fretz, Tetrahedron 54, 4849, 1998) (0.203 g, 0.604 mmol) in THF (0.5 ml). The reaction was allowed to warm slowly to room temperature, and was then 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 toluene/ethyl acetate 5% giving 0.176 g of the title compound.

Workup

  1. customwas then 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-88b879f0a0234b94b02516e1f9d2a99b
Source dataset
uspto-grants-2003_06
Patent number
US06583126B2

Reaction notes

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