Cesium carbonate → Benzyl 2'-(3-tert-butoxy-2,2-dimethyl-3-oxopropoxy)-3-fluorobiphenyl-4-carboxylate

HRID 1026558Notes

Reaction equation

HRID 1026558 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[OH:24])[CH:5]=[CH:6][C:7]=1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:32][C:33]([CH3:42])([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>CN(C)C=O>[C:37]([O:36][C:34](=[O:35])[C:33]([CH3:42])([CH3:41])[CH2:32][O:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[C:2]([F:1])[CH:3]=1)([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 68005717Benzyl 3-fluoro-2'-hydroxybiphenyl-4-carboxylateHCID 86671390Tert-butyl 3-bromo-2,2-dimethylpropanoate

Product 1

HCID 68006312Benzyl 2'-(3-tert-butoxy-2,2-dimethyl-3-oxopropoxy)-3-fluorobiphenyl-4-carboxylateYield 68.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To an N,N-dimethylformamide solution (200 ml) of benzyl 3-fluoro-2′-hydroxybiphenyl-4-carboxylate (14.8 g) was added at room temperature cesium carbonate (37.5 g), followed by stirring for 30 minutes. To this was added an N,N-dimethylformamide solution (200 ml) of tert-butyl 3-bromo-2,2-dimethylpropanoate (27.2 g), followed by stirring at 60° C. for 3 days. After the reaction solution was concentrated under reduced pressure, water and ethyl acetate were added to the residue, and the solution was separated. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford benzyl 2′-(3-tert-butoxy-2,2-dimethyl-3-oxopropoxy)-3-fluorobiphenyl-4-carboxylate (15.0 g).

Workup

  1. stirringby stirring at 60° C. for 3 days
  2. concentrationAfter the reaction solution was concentrated under reduced pressure, water and ethyl acetate
  3. additionwere added to the residue
  4. customthe solution was separated
  5. washThe organic layer was washed with saturated sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d0f06e9415fa4d2fb7c36d7a1add253d
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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