Pyridine → 2-(3-Acetylphenyl)propanenitrile

HRID 64226Notes

Reaction equation

HRID 64226 reaction equation
[CH3:1]C1(C)OC(=O)CC(=O)O1.N1C=CC=CC=1.[C:17]([CH:19]([C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24](Cl)=[O:25])[CH3:20])#[N:18]>ClCCl>[C:24]([C:23]1[CH:22]=[C:21]([CH:19]([CH3:20])[C:17]#[N:18])[CH:29]=[CH:28][CH:27]=1)(=[O:25])[CH3:1]

Participants

5

Reactant 3

HCID 1049PyridineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 30163933-(1-Cyanoethyl)benzoyl chloride

Product 1

HCID 114579542-(3-Acetylphenyl)propanenitrileYield 31.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Next, to a solution of Meldrum's acid (408 mg, 2.84 mmol) in dichloromethane (15 mL) at 0° C. was added pyridine (0.457 mL, 5.68 mmol). The resulting mixture was stirred for 15 min and then 3-(1-cyanoethyl)benzoyl chloride (482.5 mg, 2.5 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min and then for 1 h at room temperature. The reaction mixture was diluted with dichloromethane and washed with 1 N HCl. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was dissolved in AcOH—H2O (1:2) and heated at reflux for 4 h. The reaction mixture was diluted with water and extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with NaHCO3 solution and brine, then dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography using hexane-ethyl acetate (9:1) as eluent to give 13 (138 mg, 28%). 1H NMR (CDCl3, 400 MHz) δ 1.68 (d, J=7.2 Hz 3H), 2.63 (s, 3H), 3.99 (q, J=7.2 Hz, 1H), 6.60 (d, J=7.6 Hz, 1H), 7.53 (d, J=2.8 Hz, 1H), 7.60 (d, J=7.2 Hz, 1H), 7.91 (t, J=2 Hz, 1H), 7.94 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 30 min
  2. waitfor 1 h at room temperature
  3. washwashed with 1 N HCl
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe crude product was dissolved in AcOH—H2O (1:2)
  8. temperatureheated
  9. temperatureat reflux for 4 h
  10. additionThe reaction mixture was diluted with water
  11. extractionextracted with ethyl acetate (3×30 mL)
  12. washThe combined organic extracts were washed with NaHCO3 solution and brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-8ea80cf0c43b432b9eecde77e610a01e
Source dataset
uspto-grants-2016_09
Patent number
US09447134B2

Reaction notes

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