3-Chloro-4-fluoroaniline → 3-chloro-N-(3-chloro-4-fluorophenyl)propanamide

HRID 344851Notes

Reaction equation

HRID 344851 reaction equation
[Cl:1][CH2:2][CH2:3][C:4](Cl)=[O:5].[Cl:7][C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=1[F:15])[NH2:11]>CC(C)=O>[Cl:7][C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=1[F:15])[NH:11][C:4](=[O:5])[CH2:3][CH2:2][Cl:1]

Participants

4

Reactant 2

HCID 97083-Chloro-4-fluoroanilineHCID 693643-Chloropropionyl chloride

Product 1

HCID 45817873-chloro-N-(3-chloro-4-fluorophenyl)propanamideYield 74.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 3-chloropropionyl chloride (127 g) in acetone (200 cc) is added with stirring in the course of 35 minutes to a solution, at a temperature in the region of 55°) C., of 3-chloro-4-fluoroaniline (291 g) in acetone (500 cc), and the mixture is maintained at this temperature for 2 hours. After cooling to approximately 20° C., the insoluble matter is removed by filtration and washed with acetone (2×200 cc). The combined filtrate and washings are poured with stirring into water (2 liters) and ice (1 kg). The temperature is allowed to rise to approximately 20° C. and the product is extracted with dichloromethane (4×500 cc). The combined organic extracts are washed with water (3×500 cc), dried over magnesium sulphate, stirred for 15 minutes with Norit vegetable charcoal (6 g), filtered through diatomaceous silica for filtration and concentrated under reduced pressure (2.7 kPa) at 50° C. The solid obtained is recrystallized in a mixture of cyclohexane (133 cc) and isopropyl ether (67 cc). 3'-Chloro-4'-fluoro-3-chloropropionanilide (176 g) is obtained in the form of a beige solid, m.p. 94° C., which is used without further treatment for the subsequent steps.

Workup

  1. customthe insoluble matter is removed by filtration
  2. washwashed with acetone (2×200 cc)
  3. additionThe combined filtrate and washings are poured
  4. stirringwith stirring into water (2 liters) and ice (1 kg)
  5. customto rise to approximately 20° C.
  6. extractionthe product is extracted with dichloromethane (4×500 cc)
  7. washThe combined organic extracts are washed with water (3×500 cc)
  8. dry with materialdried over magnesium sulphate
  9. stirringstirred for 15 minutes with Norit vegetable charcoal (6 g)
  10. filtrationfiltered through diatomaceous silica for filtration
  11. concentrationconcentrated under reduced pressure (2.7 kPa) at 50° C
  12. customThe solid obtained
  13. customis recrystallized in a mixture of cyclohexane (133 cc) and isopropyl ether (67 cc)

Sources & evidence

ORD record
ord-abf0ea55fb5d46da952161ec2f8c1cc9
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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