Methyl iodide → Methyl 2,4-dichloropyridine-3-carboxylate

HRID 1398333Notes

Reaction equation

HRID 1398333 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([OH:6])=[O:5].[CH2:12]1CCN2C(=NCCC2)CC1.CI>C(#N)C>[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([O:6][CH3:12])=[O:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 105838872,4-Dichloronicotinic Acid

Product 1

HCID 27282740Methyl 2,4-dichloropyridine-3-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2,4-dichloronicotinic acid (500 mg, 2.60 mmol) in acetonitrile (10 mL) cooled to 0° C. was added DBU (0.981 mL, 6.51 mmol) followed by methyl iodide (0.814 mL, 13.0 mmol). The reaction mixture was stirred at RT overnight (14 h). After the reaction completion, the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (10 mL) and washed with water (1×5 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc-hexane) to afford methyl 2,4-dichloronicotinate (260 mg, 1.262 mmol, 49% yield) as pale yellow oil. LC/MS, (ESI) m/z 206.1 [(M+H)+, calcd for C7H6Cl2NO2 205.97]; LC/MS retention time (method D): tR=0.85 min. 1H NMR (300 MHz, CD3OD) δ ppm 8.42 (d, J=5.4 Hz, 1H), 7.59 (d, J=5.4 Hz, 1H), 3.99 (s, 3H).

Workup

  1. customAfter the reaction completion, the solvent was removed under reduced pressure
  2. washwashed with water (1×5 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (EtOAc-hexane)

Sources & evidence

ORD record
ord-b9335b01119a4086a0d13e8bbda76918
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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