Toluene → HCID 86758113, compound

HRID 2184910Notes

Reaction equation

HRID 2184910 reaction equation
FC(F)(F)COP([CH2:13][C:14]([O:16][CH3:17])=[O:15])(=O)OCC(F)(F)F.C1OCCOCCOCCOCCOCCOC1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[N:55]1([CH2:60][C:61]([C:63]2[CH:64]=[C:65]([CH:68]=[CH:69][CH:70]=2)[C:66]#[N:67])=O)[CH:59]=[CH:58][CH:57]=[N:56]1>O1CCCC1>[C:66]([C:65]1[CH:64]=[C:63](/[C:61](/[CH2:60][N:55]2[CH:59]=[CH:58][CH:57]=[N:56]2)=[CH:13]\[C:14]([O:16][CH3:17])=[O:15])[CH:70]=[CH:69][CH:68]=1)#[N:67]

Participants

7

Reactant 5

HCID 1140TolueneHCID 2855718-Crown-6HCID 184894Nsc 634137HCID 3251421Potassium bis(trimethylsilyl)amideHCID 224583253-[2-(1H-1-pyrazolyl)acetyl]benzonitrile

Product 1

HCID 86758113HCID 86758113, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of bis(2,2,2-trifluoroethyl)(methoxycarbonylmethyl)phosphonate (0.39 ml, 1.87 mmol) in 5 ml anhydrous tetrahydrofuran was added a solution of 18-crown-6 (2 g, 7.8 mmol) in 5 ml anhydrous tetrahydrofuran. Reaction was cooled to −78° C. to which a 0.5M solution of potassium bis(trimethylsilyl)amide in toluene (0.93 ml, 1.87 mmol) was added all at once. The reaction mixture was stirred at −78° C. for 20 minutes after which a solution of 3-[2-(1H-1-pyrazolyl)acetyl]-benzonitrile (330 mg, 1.56 mmol) in 5 ml anhydrous tetrahydrofuran was added dropwise over several minutes. Reaction was gradually allowed to warm to room temperature and stirred for 5 hours. Reaction was then quenched with a saturated ammonium chloride solution (10 ml) and extracted with 2×25 ml diethyl ether. Combined organic layers were washed with 2×25 ml water, 2×25 ml saturated brine solution, dried over magnesium sulfate, filtered and concentrated to a brown residue. Crude residue was chromatographed on silica gel using a gradient of 5% EtOAc in hexane containing 0.1% triethylamine to 20% EtOAc in hexane containing 0.1% triethylamine to give methyl (E)-3-(3-cyanophenyl)-4-(1H-1-pyrazolyl)-2-butenoate (135 mg, 32%) as a clear oil after drying. H1NMR (CDCl3) 3.521 (s, #H); 4.98 (s, 2H); 5.694 (s, H); 6.237-6.247 (t, H); 7.296-7.593 (m, 6H). NOE experiment confirmed the stereochemical configuration.

Workup

  1. customReaction
  2. additionwas added all at once
  3. additionwas added dropwise over several minutes
  4. customReaction
  5. customReaction
  6. customwas then quenched with a saturated ammonium chloride solution (10 ml)
  7. extractionextracted with 2×25 ml diethyl ether
  8. washCombined organic layers were washed with 2×25 ml water, 2×25 ml saturated brine solution
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to a brown residue
  12. customCrude residue was chromatographed on silica gel using a gradient of 5% EtOAc in hexane containing 0.1% triethylamine to 20% EtOAc in hexane containing 0.1% triethylamine

Sources & evidence

ORD record
ord-7f613f7771034b96bd66a53f88db19a7
Source dataset
uspto-grants-2002_06
Patent number
US06399627B1

Reaction notes

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