Hydrochloric Acid → 1-(2-Amino-3-chlorophenyl)-2-chloroethan-1-one

HRID 1371864Notes

Reaction equation

HRID 1371864 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].B(Cl)(Cl)Cl.[Cl:13][CH2:14][C:15]#N.[Cl-].[Cl-].[Cl-].[Al+3].Cl.[OH-:22].[Na+]>C1(C)C=CC=CC=1.ClCCl>[NH2:4][C:3]1[C:2]([Cl:1])=[CH:8][CH:7]=[CH:6][C:5]=1[C:15](=[O:22])[CH2:14][Cl:13]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 72402-ChloroanilineHCID 7856ChloroacetonitrileHCID 14798Sodium HydroxideHCID 25135Boron TrichlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 124777781-(2-Amino-3-chlorophenyl)-2-chloroethan-1-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

By the method of J. Med. Chem. 1990, 33, 2777), add dropwise 2-chloroaniline (5.8 g, 45.45 mmol) in anhydrous toluene (80 mL) to a cold 1M solution of BCl3 (50 mL) in dichloromethane. After addition, allow the reaction to stir at 0° C. for 10 minutes. After 10 minutes at 0° C., add chloroacetonitrile (13.72 g, 11.53 mL, 181.8 mmol, 4 eq) and aluminum trichloride (6.67 g, 50 mmol, 1.1 eq) in 5 equal portions over 45 minutes and then heat to reflux (˜65° C.). After 6 hours, cool to room temperature. After 16 hours, cool the reaction in an ice bath and add 2N HCl (61.4 mL) and then heat the reaction to reflux. After 45 minutes, cool in an ice bath, neutralize the acid with 2N NaOH keeping the temperature of the reaction below 15° C. until the pH is about 5. Transfer the reaction to a separatory funnel and remove the organic layer. Extract the aqueous layer with dichloromethane (2×200 mL). Combine the organic layers, dry over MgSO4, filter, and remove the solvent in vacuo to give 1-(2-amino-3-chlorophenyl)-2-chloroethanone which may be used without further purification.

Workup

  1. additionAfter addition
  2. customthe reaction
  3. waitAfter 10 minutes at 0° C.
  4. temperatureheat
  5. temperatureto reflux (˜65° C.)
  6. waitAfter 6 hours
  7. temperaturecool to room temperature
  8. waitAfter 16 hours
  9. temperaturecool
  10. customthe reaction in an ice bath
  11. temperatureheat
  12. customthe reaction
  13. temperatureto reflux
  14. waitAfter 45 minutes
  15. temperaturecool in an ice bath
  16. customthe temperature of the reaction below 15° C. until the pH is about 5
  17. customthe reaction to a separatory funnel
  18. customremove the organic layer
  19. extractionExtract the aqueous layer with dichloromethane (2×200 mL)
  20. dry with materialCombine the organic layers, dry over MgSO4
  21. filtrationfilter
  22. customremove the solvent in vacuo

Sources & evidence

ORD record
ord-a001a10cc5554124aac184c120fd3d3c
Source dataset
uspto-grants-2007_01
Patent number
US07157488B2

Reaction notes

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