Cesium fluoride → 6-[5-(6-Chloro-2-methylpyridin-3-yl)-2-ethylphenyl]-2,2,4,4-tetramethylcyclohexane-1,3,5-trione

HRID 1191585Notes

Reaction equation

HRID 1191585 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:21][CH3:22])=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[C:11](=[O:17])[C:10]([CH3:19])([CH3:18])[C:9]2=[O:20])[CH:7]=1.[F-].[Cs+].[Cl:25][C:26]1[N:31]=[C:30]([CH3:32])[C:29](B(O)O)=[CH:28][CH:27]=1>ClCCl.O>[Cl:25][C:26]1[N:31]=[C:30]([CH3:32])[C:29]([C:2]2[CH:3]=[CH:4][C:5]([CH2:21][CH3:22])=[C:6]([CH:8]3[C:13](=[O:14])[C:12]([CH3:15])([CH3:16])[C:11](=[O:17])[C:10]([CH3:19])([CH3:18])[C:9]3=[O:20])[CH:7]=2)=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 441191526-Chloro-2-methylpyridine-3-boronic acidHCID 684845366-(5-Bromo-2-ethylphenyl)-2,2,4,4-tetramethylcyclohexane-1,3,5-trione

Product 1

HCID 866443106-[5-(6-Chloro-2-methylpyridin-3-yl)-2-ethylphenyl]-2,2,4,4-tetramethylcyclohexane-1,3,5-trioneYield 36.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-(5-bromo-2-ethylphenyl)-2,2,4,4-tetramethylcyclohexane-1,3,5-trione (0.19 g, 0.5 mmol), cesium fluoride (0.24 g, 1.6 mmol), 6-chloro-2-methylpyridin-3-ylboronic acid (0.13 g, 0.8 mmol) and degassed 1,2-dimethoxyethane (1.7 ml) is stirred under nitrogen at room temperature for 30 minutes. [1,1′-Bis-(diphenylphosphino)ferrocene]dichloro-palladium(II) (0.034 g, 0.042 mmol) is added and the mixture is stirred at room temperature for 10 minutes and then heated at 80° C. overnight. After cooling to room temperature the reaction mixture is diluted with dichloromethane (5 ml) and water and filtered through diatomaceous earth. The filtrate is acidified with 2M aqueous hydrochloric acid, and the organic phase is separated, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue is dissolved in N,N-dimethylformamide (approximately 1 ml) and purified by preparative reverse phase HPLC to afford 6-[5-(6-chloro-2-methylpyridin-3-yl)-2-ethylphenyl]-2,2,4,4-tetramethylcyclohexane-1,3,5-trione as a pale brown solid (75.3 mg).

Workup

  1. customdegassed 1,2-dimethoxyethane (1.7 ml)
  2. stirringthe mixture is stirred at room temperature for 10 minutes
  3. temperatureheated at 80° C. overnight
  4. temperatureAfter cooling to room temperature the reaction mixture
  5. filtrationfiltered through diatomaceous earth
  6. customthe organic phase is separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue is dissolved in N,N-dimethylformamide (approximately 1 ml)
  10. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-5dec77f64af94d1c8a83fcd4b0afd03f
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

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