Cesium carbonate → (1S,2S)-2-{4-[(R)-4-(4-Cyano-phenoxy)-7-fluoro-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester

HRID 625695Notes

Reaction equation

HRID 625695 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([OH:26])[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].F[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:10]=[CH:11][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:28]4[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:13][CH:14]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 145174-FluorobenzonitrileHCID 118093712(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester2×

Product 1

HCID 118093725(1S,2S)-2-{4-[(R)-4-(4-Cyano-phenoxy)-7-fluoro-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl esterYield 33.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester (Intermediate 5, 146 mg, 0.41 mmol), 4-fluorobenzonitrile (55 mg, 0.45 mmol), and cesium carbonate (145 mg, 0.45 mmol) are suspended in dry dimethylformamide (10 mL) and stirred for 3 hours at 100° C. followed by room temperature overnight. The mixture is diluted with water and extracted with ethyl acetate. The organic extract is dried over sodium sulfate, filtered and the solvent removed. The residue is purified by flash chromatography (10% ethyl acetate in cyclohexane) to give the title compound (Yield 62 mg). LC (METHOD 5): tR=1.54 min; Mass spectrum (ES+): m/z=458 [M+H]+.

Workup

  1. waitfollowed by room temperature overnight
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. dry with materialis dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed
  7. customThe residue is purified by flash chromatography (10% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-c98f214efd9d4626aae482d7647e4705
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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