Dimethylformamide → benzyl 2'-{[(2S)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpropyl]oxy}-3-fluorobiphenyl-4-carboxylate

HRID 1026569Notes

Reaction equation

HRID 1026569 reaction equation
CN(C)C=O.[F:6][C:7]1[CH:8]=[C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[OH:29])[CH:10]=[CH:11][C:12]=1[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].Br[CH2:31][C@H:32]([CH3:52])[CH2:33][O:34][Si:35]([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(OCC)(=O)C>[Si:35]([O:34][CH2:33][C@@H:32]([CH3:52])[CH2:31][O:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])=[C:7]([F:6])[CH:8]=1)([C:48]([CH3:49])([CH3:50])[CH3:51])([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 68005717Benzyl 3-fluoro-2'-hydroxybiphenyl-4-carboxylateHCID 69007455((R)-3-bromo-2-methylpropoxy)-tert-butyldiphenylsilane

Product 1

HCID 68006513benzyl 2'-{[(2S)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpropyl]oxy}-3-fluorobiphenyl-4-carboxylateYield 76.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To an N,N-dimethylformamide solution (30 ml) of benzyl 3-fluoro-2′-hydroxybiphenyl-4-carboxylate (Example 1-3) (1.0 g) and {[(2R)-3-bromo-2-methylpropyl]oxy}(tert-butyl)diphenylsilane (1.5 g) was added at room temperature cesium carbonate (2.4 g), followed by stirring at 60° C. for 1 hour. Ethyl acetate and water were added to the reaction solution, 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′-{[(2S)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-methylpropyl]oxy}-3-fluorobiphenyl-4-carboxylate (1.5 g).

Workup

  1. customthe solution was separated
  2. washThe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2cb2a03b3df64b99bead2feb82365b60
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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