Cesium carbonate → methyl ((1R)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2098966Notes

Reaction equation

HRID 2098966 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C@H:8]2[CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:22]([O:26][C:27]1[CH:32]=[C:31]([CH2:33]Cl)[CH:30]=[CH:29][C:28]=1[C:35]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:36]=1[F:43])[CH2:23][CH2:24][CH3:25]>CN(C=O)C.O>[CH2:22]([O:26][C:27]1[CH:32]=[C:31]([CH2:33][O:1][C:2]2[CH:10]=[C:9]3[C:5]([CH2:6][CH2:7][C@@H:8]3[CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=2)[CH:30]=[CH:29][C:28]=1[C:35]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:36]=1[F:43])[CH2:23][CH2:24][CH3:25].[CH2:22]([O:26][C:27]1[CH:32]=[C:31]([CH2:33][O:1][C:2]2[CH:10]=[C:9]3[C:5]([CH2:6][CH2:7][C@H:8]3[CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=2)[CH:30]=[CH:29][C:28]=1[C:35]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:36]=1[F:43])[CH2:23][CH2:24][CH3:25]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 577055582-(Butyloxy)-4-(chloromethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenylHCID 59590768(S)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate

Product 2

HCID 59590805methyl ((1R)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetateHCID 59590932methyl ((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To flask containing (R) or (S)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate (1.5) (0.0100 g, 0.0485 mmol) and cesium carbonate (0.0205 g, 0.0630 mmol) in DMF (1 mL) was added 2-(butyloxy)-4-(chloromethyl)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl (D) (0.0188 g, 0.0582 mmol). The reaction was then stirred overnight, diluted with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, concentrated, and then purified by silica gel chromatography (0 to 20% EtOAc/Hexane) to provide methyl ((1R)-6-(((2-(butyloxy)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetate or methyl ((1S)-6-(((2-(butyloxy)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetate 17.1.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (0 to 20% EtOAc/Hexane)

Sources & evidence

ORD record
ord-87a18c18aeab42adaa71d95634b76307
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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