Sodium hydride → N-[4-(E-2-Cyano-2-pyrid-3-ylethenyl)-2-(2-methylphenyl)benzoyl]methionine, Methyl Ester

HRID 2121272Notes

Reaction equation

HRID 2121272 reaction equation
CCOP(O[CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1)[C:10]#[N:11])(CC)=O.[H-].[Na+].[CH3:20][O:21][C:22](=[O:46])[C@H:23]([CH2:42][CH2:43][S:44][CH3:45])[NH:24][C:25](=[O:41])[C:26]1[CH:31]=[CH:30][C:29]([CH:32]=O)=[CH:28][C:27]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:40]>COCCOC>[C:10](/[C:9](/[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[CH:32]/[C:29]1[CH:30]=[CH:31][C:26]([C:25]([NH:24][C@H:23]([C:22]([O:21][CH3:20])=[O:46])[CH2:42][CH2:43][S:44][CH3:45])=[O:41])=[C:27]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH:28]=1)#[N:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10596254HCID 10596254, compoundHCID 88040914Diethyl 3-pyridylcyanomethyl phosphonate

Product 1

HCID 20622898N-[4-(E-2-Cyano-2-pyrid-3-ylethenyl)-2-(2-methylphenyl)benzoyl]methionine, Methyl Ester

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of diethyl 3-pyridylcyanomethyl phosphonate (269 mg) in DME (3 mL) was added NaH (39 mg@60%). To the red solution was added N-[4-formyl-2-(2-methylphenyl)benzoyl] methionine methyl ester (example 10756, 340 mg). After 30 min, the reaction was warmed to reflux for 2.5 h. The reaction was cooled, quenched with water (5 mL), and extracted into EtOAc (20 mL). The organic extracts were washed with brine (5 mL), dried (MgSO4), filtered and concentrated. The residue was purified by silica gel chromatography eluting with 50%-100% EtOAc/hexane to afford two products as colorless oils. The more mobile isomer (68 mg, 13%) was assigned the Z configuration based on a ROESY experiment. MS (APCI(+)) m/e 486 (M+H)+. MS (APCI(−)) m/e 485 M−. The less mobile isomer (246 mg, 48%) was assigned the E configuration based on a ROESY experiment. MS (APCI(+)) m/e 486 (M+H)+. MS (APCI(−)) m/e 485 M−.

Workup

  1. temperaturethe reaction was warmed
  2. temperatureto reflux for 2.5 h
  3. temperatureThe reaction was cooled
  4. customquenched with water (5 mL)
  5. extractionextracted into EtOAc (20 mL)
  6. washThe organic extracts were washed with brine (5 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with 50%-100% EtOAc/hexane
  12. customto afford two products as colorless oils

Sources & evidence

ORD record
ord-167a51ac699c47d6a3cc6d903a5fc671
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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