3-Chloroaniline → HCID 68893141, compound

HRID 1760596Notes

Reaction equation

HRID 1760596 reaction equation
N([O-])=O.[Na+].[Cl:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][CH:12]=1)[NH2:9].C([O-])(=O)C.[Na+].[CH2:18]([CH:20]([C:26]([CH3:28])=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH3:19].[OH-].[K+]>O.Cl.C(O)C>[Cl:5][C:6]1[CH:7]=[C:8]2[C:10]([C:18]([CH3:20])=[CH:19][NH:9]2)=[CH:11][CH:12]=1.[CH2:24]([O:23][C:21]([C:20]1[NH:9][C:8]2[C:28]([CH:26]=1)=[CH:11][CH:12]=[CH:6][CH:7]=2)=[O:22])[CH3:25]

Participants

9

Reactant 5

HCID 79323-ChloroanilineHCID 14797Potassium HydroxideHCID 79065Butanoic acid, 2-ethyl-3-oxo-, ethyl esterHCID 517045Sodium AcetateHCID 23668193Sodium Nitrite

Product 1

HCID 68893141HCID 68893141, compoundYield 29.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of sodium nitrite (5.95 g, 86.2 mmol) in water (7 mL) was added dropwise at −5° C. to a mixture of 3-chloroaniline (10.0 g, 78.4 mmol) in water (27 mL) and 37% aq. hydrochloric acid solution (16 mL), then after 15 min sodium acetate (5.47 g, 66.6 mmol) was added. In a separate flask a solution of ethyl α-ethylacetoacetate (13.6 g, 86.2 mmol) in ethanol (50 mL) was treated with with a solution of 85% potassium hydroxide (5.69 g, 86.2 mmol) in water (6 mL) at 0° C., then ice (80 g) and the above prepared aryldiazonium solution were rapidly added. The two-phase mixture obtained was stirred 3 h at 0° C., and kept at 4° C. overnight, then extracted with ethyl acetate (2×200 mL). The organic layer was washed with brine, dried (MgSO4), and evaporated. The resultant red oil was added within 30 min to a boiling mixture of ethanol (100 mL) and acetyl chloride (25 mL). After 2 h at reflux, the mixture was cooled to room temperature then filtered. The filtrate was evaporated then partitioned between water and chloroform. The organic layer was washed with sat. aq. sodium hydrogen carbonate solution and brine, dried (MgSO4), and evaporated. The solid was successively triturated in dichloromethane/hexane 1:1 (100 mL) and ether (50 mL, twice) to afford the title compound (4.06 g, 22%). White solid, EI-MS: m/e=237.1 (M+).

Workup

  1. additionwere rapidly added
  2. customThe two-phase mixture obtained
  3. waitkept at 4° C. overnight
  4. extractionextracted with ethyl acetate (2×200 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. additionThe resultant red oil was added within 30 min to a boiling mixture of ethanol (100 mL) and acetyl chloride (25 mL)
  9. temperatureAfter 2 h at reflux
  10. temperaturethe mixture was cooled to room temperature
  11. filtrationthen filtered
  12. customThe filtrate was evaporated
  13. customthen partitioned between water and chloroform
  14. washThe organic layer was washed with sat. aq. sodium hydrogen carbonate solution and brine
  15. dry with materialdried (MgSO4)
  16. customevaporated
  17. customThe solid was successively triturated in dichloromethane/hexane 1:1 (100 mL)

Sources & evidence

ORD record
ord-dc7583a1c3f046bd96545b2a8b496697
Source dataset
uspto-grants-2005_01
Patent number
US06844345B2

Reaction notes

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