Cesium carbonate → 4-(2-Cyclopropyl-2-oxoethoxy)-2,6-dimethylbenzonitrile

HRID 31157Notes

Reaction equation

HRID 31157 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:15]=[C:14]([CH3:16])[C:11]([C:12]#[N:13])=[C:10]([CH3:17])[CH:9]=1.Br[CH2:19][C:20]([CH:22]1[CH2:24][CH2:23]1)=[O:21]>CC(C)=O>[CH:22]1([C:20](=[O:21])[CH2:19][O:7][C:8]2[CH:9]=[C:10]([CH3:17])[C:11]([C:12]#[N:13])=[C:14]([CH3:16])[CH:15]=2)[CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5901834-Hydroxy-2,6-dimethylbenzonitrileHCID 109208412-Bromo-1-cyclopropylethan-1-one

Product 1

HCID 590181944-(2-Cyclopropyl-2-oxoethoxy)-2,6-dimethylbenzonitrileYield 94.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

Cesium carbonate (30.7 g, 111.16 mmol) was added to a solution of 4-hydroxy-2,6-dimethylbenzonitrile (15.27 g, 101.89 mmol), in acetone (377 ml). Then 2-bromo-1-cyclopropylethanone (15.1 g, 62.6 mmol), in acetone (100 ml), was added dropwise, over 5 minutes, to the suspension and the reaction mixture was heated at reflux for 1.5 hours. The reaction mixture was then concentrated under reduced pressure and the residue was partitioned between a saturated aqueous solution of potassium carbonate (300 ml) and dichloromethane (300 ml). The organic layer was separated and washed with brine (250 ml), dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:pentane (50:50 to 80:20, by volume) to provide the title compound (13.5 g, 64%) as a solid. 1H-NMR (400 MHz, CDCl3): δ=0.97-1.01 (m, 2H), 1.12-1.15 (m, 2H), 2.19 (m, 1H), 2.47 (s, 6H), 4.71 (s, 2H), 6.61 (s, 2H); LRMS: APCl+: 230 [MH+]

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 1.5 hours
  3. concentrationThe reaction mixture was then concentrated under reduced pressure
  4. customthe residue was partitioned between a saturated aqueous solution of potassium carbonate (300 ml) and dichloromethane (300 ml)
  5. customThe organic layer was separated
  6. washwashed with brine (250 ml)
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:pentane (50:50 to 80:20, by volume)

Sources & evidence

ORD record
ord-4708472473954e7cb4c7d88db49c610c
Source dataset
uspto-grants-2008_09
Patent number
US07425569B2

Reaction notes

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