Oxalyl chloride → Methyl 6-chloropyridine-3-carboxylate

HRID 1255889Notes

Reaction equation

HRID 1255889 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[C:11](Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:11])=[O:7])=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 792226-Chloronicotinic acid

Product 1

HCID 254249Methyl 6-chloropyridine-3-carboxylateYield 96.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-chloronicotinic acid (20.0 g, 0.127 mol) in CH2Cl2 (250 mL) was added oxalyl chloride (123.3 mL, 0.15 mol) with 1-5 drops of DMF. The solution was stirred 18 h and concentrated in vacuo. The residue was dissolved in CH2Cl2 (100 mL) and cooled in an ice bath. To this was added MeOH (20 mL) and the solution was stirred for 15 min while maintaining a temp below 40° C. The solvent was removed in vacuo, and the residue was dissolved in Et2O, washed with H2O and brine, dried with Na2SO4, and filtered through SiO2. The solvent was removed in vacuo to yield 6-chloronicotinic acid, methyl ester (21 g) as an off-white solid: 1H-NMR (300 MHz, CDCl3) δ 9.02 (d, J=13.8 Hz, 1H), 8.51-8.06 (m, 1H), 7.76-7.30 (m, 1H), 4.01 (s, 3H); EIMS m/z 171 ([M]+), which was used in Step 2 without further purification.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (100 mL)
  3. temperaturecooled in an ice bath
  4. additionTo this was added MeOH (20 mL)
  5. stirringthe solution was stirred for 15 min
  6. temperaturewhile maintaining a temp below 40° C
  7. customThe solvent was removed in vacuo
  8. dissolutionthe residue was dissolved in Et2O
  9. washwashed with H2O and brine
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered through SiO2
  12. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-b06d0d21c93347f8a987d3421d441847
Source dataset
uspto-grants-2013_06
Patent number
US08461164B2

Reaction notes

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