Sodium hydride → HCID 58780780, compound

HRID 747146Notes

Reaction equation

HRID 747146 reaction equation
[H-].[Na+].[C:3]([CH2:5]P(=O)(OCC)OCC)#[N:4].Br[C:15]1[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[N:19][CH:20]=1.[F:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH:27]=O>COCCOC.[Cl-].[NH4+].C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:23][C:24]1[CH:25]=[C:26](/[CH:27]=[C:5](\[C:15]2[CH:20]=[N:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)/[C:3]#[N:4])[CH:29]=[CH:30][CH:31]=1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 680093-FluorobenzaldehydeHCID 75676Diethyl (cyanomethyl)phosphonateHCID 27348955-Bromo-2-methoxypyridine

Product 1

HCID 58780780HCID 58780780, compoundYield 29%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of sodium hydride (8.8 g, 0.220 mol) in 1,2-dimethoxyethane (300 ml) was added diethyl cyanomethylphosphonate (19.7 g, 0.122 mol) little by little at room temperature under an atmosphere of nitrogen gas. After stirring for 15 minutes, 5-bromo-2-methoxypyridine (20.0 g, 0.106 mol) and tetrakis(triphenylphosphine)palladium (0) (2.0 g, 1.73 mmol) were successively added thereto, followed by heating to 90° C. and stirring for 6 hours. The reaction mixture was cooled as it was and further ice-cooled. 3-Fluorobenzaldehyde (13.7 g, 0.110 mol) was added dropwise thereto over 1.5 hours at 1 to 4° C. under an atmosphere of nitrogen gas, followed by stirring further for 2.5 hours while gradually elevating to room temperature. The reaction mixture was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate, and then the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous ammonium chloride solution twice, dried over anhydrous sodium sulfate and then concentrated. The residue was suspended in methanol, and then the resulting solid was collected by filtration and washed with diethyl ether and hexane, to give the title compound (7.80 g, 29%) as a colorless solid.

Workup

  1. stirringstirring for 6 hours
  2. temperatureThe reaction mixture was cooled as it
  3. temperaturefurther ice-cooled
  4. waitover 1.5 hours at 1 to 4° C. under an atmosphere of nitrogen gas
  5. stirringby stirring further for 2.5 hours
  6. customwhile gradually elevating to room temperature
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. washThe combined organic layers were washed with a saturated aqueous ammonium chloride solution twice
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. filtrationthe resulting solid was collected by filtration
  12. washwashed with diethyl ether and hexane

Sources & evidence

ORD record
ord-6111a449b76040c8836b89480a26f5a4
Source dataset
uspto-grants-2008_07
Patent number
US07396836B2

Reaction notes

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