Cesium carbonate → 3-(4,4-Difluoro-1'-oxo-1',3'-dihydrospiro[cyclohexane-1,2'-indene]-6'-yl)benzonitrile

HRID 472966Notes

Reaction equation

HRID 472966 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][CH:3]=1.[C:19]([C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1)#[N:20].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:17][C:14]1([F:18])[CH2:15][CH2:16][C:7]2([CH2:6][C:5]3[C:9](=[CH:10][C:2]([C:25]4[CH:26]=[C:21]([CH:22]=[CH:23][CH:24]=4)[C:19]#[N:20])=[CH:3][CH:4]=3)[C:8]2=[O:11])[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343253-Cyanophenylboronic acidHCID 581972726'-bromo-4,4-difluorospiro[cyclohexane-1,2'-inden]-1'(3'H)-one

Product 1

HCID 665849403-(4,4-Difluoro-1'-oxo-1',3'-dihydrospiro[cyclohexane-1,2'-indene]-6'-yl)benzonitrileYield 80.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

In a 20 mL vial was placed 6′-bromo-4,4-difluorospiro[cyclohexane-1,2′-inden]-1′(3′H)-one (35 mg, 0.111 mmol), 3-cyanobenzeneboronic acid (23 mg, 0.157 mmol), PdCl2(PPh3)2 (8 mg, 0.011 mmol) and cesium carbonate (91 mg, 0.279 mmol). This solid mixture was dissolved in a Dioxane/water mixture (1.1 mL, 6:1 ratio, respectively). The reaction vial was capped and allowed to stir at 90° C. for 1 hour. At this time, the mixture was filtered through a Celite plug. The plug was rinsed with dichloromethane (5 mL) and water (5 mL). The phases in the filtrate were separated. The aqueous phase was back-extracted with dichloromethane twice (3 mL/each). The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated under reduce pressure. The crude material was purified by flash chromatography (ISCO, 12 g SiO2 cartridge, ethyl acetate/hexanes as the eluents). The corresponding fractions were combined and concentrated under reduce pressure yielding 3-(4,4-difluoro-1′-oxo-1′,3′-dihydrospiro[cyclohexane-1,2′-indene]-6′-yl)benzonitrile (30 mg, 0.089 mmol, 80% yield) as a white solid.

Workup

  1. customThe reaction vial was capped
  2. filtrationAt this time, the mixture was filtered through a Celite plug
  3. washThe plug was rinsed with dichloromethane (5 mL) and water (5 mL)
  4. customThe phases in the filtrate were separated
  5. extractionThe aqueous phase was back-extracted with dichloromethane twice (3 mL/each)
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography (ISCO, 12 g SiO2 cartridge, ethyl acetate/hexanes as the eluents)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-956494c9f51047a696651fd687ea86be
Source dataset
uspto-grants-2014_01
Patent number
US08633212B2

Reaction notes

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