Benzoyl chloride, 3-chloro- → 3-Chloro-N-((3-Chloro-5-Fluorophenyl)Carbamothioyl)Benzamide

HRID 1776995Notes

Reaction equation

HRID 1776995 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].[S-:11][C:12]#[N:13].[K+].[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[C:21]([F:23])[CH:22]=1)[NH2:19]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:13][C:12](=[S:11])[NH:19][C:18]1[CH:20]=[C:21]([F:23])[CH:22]=[C:16]([Cl:15])[CH:17]=1)=[O:6]

Participants

5

Reactant 3

HCID 69252Benzoyl chloride, 3-chloro-HCID 516872Potassium thiocyanateHCID 27348383-Chloro-5-fluoroaniline

Product 1

HCID 1181396093-Chloro-N-((3-Chloro-5-Fluorophenyl)Carbamothioyl)BenzamideYield 99.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

3-Chlorobenzoyl chloride (200 g, 1.14 mol) was dissolved in acetonitrile (4.5 L) and the reaction vessel containing this mixture was cooled in an ice/water bath. Potassium thiocyanate (122 g, 1.26 mol, 1.10 equiv) was added to the reaction mixture. The cooling bath was removed from the reaction vessel after 15 minutes and the resulting slurry was stirred at room temperature for approximately 1 hour. Next, 3-chloro-5-fluoroaniline (138 mL, 1.37 mol, 1.2 equiv) was added as a solution in acetonitrile (138 mL) over 5 minutes. The reaction mixture was then stirred at room temperature overnight and subsequently quenched with water (4.30 L), and then stirred at room temperature for 1 hour. The resulting solid was collected by filtration and rinsed with acetonitrile/water (1/1 mixture by volume, 780 mL). The solid was dried at 60° C. in vacuo to provide 390 g (99% yield) of the title compound as a solid. 1H NMR (DMSO-d6) δ 12.5 (s, 1H), 11.9 (s, 1H), 8.01 (t, 1H, J=1.8), 7.89 (d, 1H, J=7.8), 7.69 (m, 3H), 7.56 (t, 1H, J=7.8), 7.34 (dt, 1H, J=8.7, 1.8). HPLC: >99% purity at 23.73 min.

Workup

  1. additionthe reaction vessel containing this mixture
  2. temperaturewas cooled in an ice/water bath
  3. customThe cooling bath was removed from the reaction vessel after 15 minutes
  4. stirringThe reaction mixture was then stirred at room temperature overnight
  5. customsubsequently quenched with water (4.30 L)
  6. stirringstirred at room temperature for 1 hour
  7. filtrationThe resulting solid was collected by filtration
  8. washrinsed with acetonitrile/water (1/1 mixture by volume, 780 mL)
  9. customThe solid was dried at 60° C. in vacuo

Sources & evidence

ORD record
ord-716557cbeb3a4c9996cf2c703661de3d
Source dataset
uspto-grants-2016_02
Patent number
US09266839B2

Reaction notes

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