4-Chloroaniline → 6-Chloro-N-(4-chlorophenyl)-3-pyridinecarboxamide

HRID 1514635Notes

Reaction equation

HRID 1514635 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[Cl:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([NH:25][C:24]2[CH:26]=[CH:27][C:21]([Cl:20])=[CH:22][CH:23]=2)=[O:7])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 78124-ChloroanilineHCID 81531DiisopropylethylamineHCID 27821656-Chloronicotinoyl Chloride

Product 1

HCID 27997686-Chloro-N-(4-chlorophenyl)-3-pyridinecarboxamideYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Commercially available 6-chloro-nicotinic chloride (56.8 mmol, 10 g) was dissolved in 50 ml of anhydrous CH2Cl2 and added dropwise to a solution of diisopropylethylamine (DIEA) (1.2 equivalents, 68.2 mmol, 11.67 ml) and 4-chloroaniline (1.2 equiv., 68.2 mmol, 8.70 g) in 50 ml CH2Cl2 at O° C. The mixture was stirred at room temperature for 20 h, then diluted with CH2Cl2 (200 ml) and washed with water (1×200 ml) and brine (1×100 ml). The organic layer was dried over sodium sulphate and concentrated. The crude was crystallized from diethyl ether to give 13 g of a white solid. Yield=86%. 1H NMR (CDCl3, 200 MHz) δ 7.35 (2H, d, J=8.8 Hz), 7.47 (1H, d, J=8.2 Hz), 7.58 (2H, d, J=8.8 Hz), 7.88 (1H, bs), 8.16 (1H, dd, J=8.4 Hz, J′=2.8 Hz), 8.84 (1H, d, J=2.4 Hz)

Workup

  1. washwashed with water (1×200 ml) and brine (1×100 ml)
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. concentrationconcentrated
  4. customThe crude was crystallized from diethyl ether

Sources & evidence

ORD record
ord-601f3be89f194895b534c85f494037cf
Source dataset
uspto-grants-2012_07
Patent number
US08222275B2

Reaction notes

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