Chloroacetyl chloride → HCID 178465117, compound

HRID 1912455Notes

Reaction equation

HRID 1912455 reaction equation
CCN(C(C)C)C(C)C.[Br:10][C:11]1[CH:12]=[C:13]([C:17]([NH2:24])([C:19]2[CH:23]=[CH:22][NH:21][N:20]=2)[CH3:18])[CH:14]=[CH:15][CH:16]=1.[Cl:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl.[NH4+].[Cl-]>[Br:10][C:11]1[CH:12]=[C:13]([C:17]([NH:24][C:27](=[O:28])[CH2:26][Cl:25])([C:19]2[CH:23]=[CH:22][NH:21][N:20]=2)[CH3:18])[CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 178463266HCID 178463266, compound

Product 1

HCID 178465117HCID 178465117, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

DIPEA (1.18 mL, 6.77 mmol) was added to a solution of rac-1-(3-bromo-phenyl)-1-(1H-pyrazol-3-yl)-ethylamine (1.2 g, 4.51 mmol) in DCM (20 mL) and the mixture was cooled in an ice bath. Then chloroacetyl chloride (0.40 mL, 4.96 mmol) was added and the mixture was stirred at 0° C. for 3 hours. The mixture was diluted with NH4Cl (aq. sat. solution) and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected and concentrated in vacuo. The residue was dissolved in EtOH (10 mL) and NaHCO3 (aq. sat. solution) (1 mL) and the mixture was stirred at room temperature for 30 minutes. The mixture was diluted with water and the product extracted with DCM. The combined organic layers were concentrated in vacuo to yield rac-N-[1-(3-bromo-phenyl)-1-(1H-pyrazol-3-yl)-ethyl]-2-chloro-acetamide (1.22 g, 79% yield) as a colourless oil, which was used in the next step without further purification.

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica gel; AcOEt in DCM 0/100 to 20/80)
  8. customThe desired fractions were collected
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in EtOH (10 mL)
  11. stirringNaHCO3 (aq. sat. solution) (1 mL) and the mixture was stirred at room temperature for 30 minutes
  12. additionThe mixture was diluted with water
  13. extractionthe product extracted with DCM
  14. concentrationThe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record
ord-03e8f8bb2d874e0588485f974b056891
Source dataset
uspto-grants-2013_12
Patent number
US08609660B2

Reaction notes

Loading…