Hydrochloric Acid → HCID 44600573, compound

HRID 1099461Notes

Reaction equation

HRID 1099461 reaction equation
[C:1]([O:9]C)(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.I[CH2:12][CH2:13][CH2:14][CH3:15].[OH-:16].[Na+].Cl>CC(C)=O.O.C(#N)C.C1(C)C=CC=CC=1>[CH2:12]([N:5]1[CH:4]=[CH:3][C:2]([C:1]([OH:9])=[O:8])=[CH:7][C:6]1=[O:16])[CH2:13][CH2:14][CH3:15]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10962Butyl iodideHCID 14798Sodium HydroxideHCID 227085Methyl isonicotinate

Product 1

HCID 44600573HCID 44600573, compound

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of methyl isonicotinate (540 mg, 3.94 mmol) in dry acetone (5 mL) was added 1-iodobutane (1.35 mL, 11.8 mmol) followed by toluene (1 mL). The reaction mixture was stirred at ambient temperature for 3 h and then heated to 50° C. over night. Acetonitrile (5 ml) was added and the temperature was raised to 80° C. for 5 h. The reaction mixture was allowed to cool to ambient temperature and was stirred over the week end. The solvent was removed in vacuo and the crude was purified by column chromatography using a gradient of methanol in dichloromethane with 1% acetic acid. 615 mg of the intermediate product was dissolved in water (6 mL) and dropwise added a 10 M solution of sodium hydroxide (1.149 mL, 11.49 mmol) and a 1.25 M solution of potassium ferricyanide(III) (3.06 mL, 3.83 mmol) in hot water over 2 h. The reaction mixture was stirred at ambient temperature for 4 h. 3M hydrochloric acid was added until an acidic pH was reached. The reaction mixture was extracted with ethyl acetate and the organic layer was dried over magnesium sulfate and concentrated in vacuo to yield 235 mg (40% total yield) of the title compound as a solid; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.78 (d, 1 H), 6.82 (d, 1 H), 6.53 (dd, 1 H), 3.89 (t, 2 H), 1.52-1.65 (m, 2 H), 1.18-1.34 (m, 2 H), 0.89 (t, 3 H); MS (ESI) m/z 196[M+H+], m/z 194[M−H+].

Workup

  1. temperatureheated to 50° C. over night
  2. temperaturethe temperature was raised to 80° C. for 5 h
  3. temperatureto cool to ambient temperature
  4. stirringwas stirred over the week end
  5. customThe solvent was removed in vacuo
  6. customthe crude was purified by column chromatography
  7. dissolution615 mg of the intermediate product was dissolved in water (6 mL)
  8. stirringThe reaction mixture was stirred at ambient temperature for 4 h
  9. extractionThe reaction mixture was extracted with ethyl acetate
  10. dry with materialthe organic layer was dried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customto yield

Sources & evidence

ORD record
ord-ff58220f9e8b41ea929bef5f5fd9a1d3
Source dataset
uspto-grants-2012_03
Patent number
US08143408B2

Reaction notes

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