Sodium hydride → HCID 58780780, compound

HRID 1373007Notes

Reaction equation

HRID 1373007 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([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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 178418397HCID 178418397, compoundCatalystHCID 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 gradually added diethyl cyanomethylphosphonate (19.7 g, 0.122 mol) 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 sequentially added thereto, and the mixture was heated to 90° C. and stirred for 6 hours. After standing to cool, the reaction mixture was further cooled on ice. 3-Fluorobenzaldehyde (13.7 g, 0.110 mol) was added dropwise thereinto under an atmosphere of nitrogen gas at 1° C. to 4° C. over 1.5 hours, and the mixture was stirred for further 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 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. customat room temperature
  2. stirringstirred for 6 hours
  3. temperatureto cool
  4. temperaturethe reaction mixture was further cooled on ice
  5. waitunder an atmosphere of nitrogen gas at 1° C. to 4° C. over 1.5 hours
  6. stirringthe mixture was stirred for further 2.5 hours
  7. customwhile gradually elevating to room temperature
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. washThe combined organic layers were washed with a saturated aqueous ammonium chloride solution twice
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated
  12. filtrationthe resulting solid was collected by filtration
  13. washwashed with diethyl ether and hexane

Sources & evidence

ORD record
ord-0150c9588ec441debf8cd32210ce011b
Source dataset
uspto-grants-2007_01
Patent number
US07160892B2

Reaction notes

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