Thionyl Chloride → 2-Chloronicotinoyl chloride

HRID 1072473Notes

Reaction equation

HRID 1072473 reaction equation
S(Cl)([Cl:3])=O.[Cl:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8](O)=[O:9]>CN(C=O)C.ClCCl>[Cl:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([Cl:3])=[O:9]

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 762582-Chloronicotinic acid

Product 1

HCID 27745412-Chloronicotinoyl chloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Thionyl chloride (2.48 ml, 10 eq) and DMF (2 drops) were added to a solution of 2-chloronicotinic acid (535 mg, 3.4 mmol) in dichloromethane (3 ml). The mixture was heated at reflux overnight then concentrated in vacuo and azeotroped with toluene (2×5 ml) to give 2-chloronicotinoyl chloride as a yellow oil. A solution of this acid chloride in dichloromethane (5 ml) was added dropwise to a solution of Intermediate 5 (750 mg, 2.69 mmol) and NMM (355 μl, 1.2 eq) in dichloromethane (15 ml) at 00. Dimethylaminopyridine (catalytic) was added and the mixture stirred at room temperature for 2 h. The mixture was then concentrated in vacuo. The residue was dissolved in ethyl acetate (50 ml) and washed with aqueous NaHCO3 (2×50 ml). The organic phase was dried (MgSO4) and concentrated in vacuo, to give the title compound. δH (CDCl3) 10.55 (1H, s), 8.51 (1H, m), 8.05 (1H, m), 7.67 (1H, m), 7.57 (3H, m), 7.2 (2H, m), 4.24 (1H, m), 3.62 (3H, s), 3.08 (2H, m), 1.03 (9H, s); m/z (ESI, 70V) 418 (M++H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. concentrationthen concentrated in vacuo
  4. customazeotroped with toluene (2×5 ml)

Sources & evidence

ORD record
ord-7e47754f36f04ed4a8d927066959d3e0
Source dataset
uspto-grants-2005_06
Patent number
US06911451B1

Reaction notes

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