2-Bromoaniline → ethyl 7-bromo-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate

HRID 576239Notes

Reaction equation

HRID 576239 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].N([O-])=[O:10].[Na+].[C:13]([O-])(=O)[CH3:14].[Na+].[CH2:18]([O:20][C:21]([CH:23]1[CH2:27][CH2:26][CH2:25][C:24]1=[O:28])=[O:22])[CH3:19]>Cl.O>[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:3]=1[NH:4][C:25]([C:24]([O:28][CH2:13][CH3:14])=[O:10])=[C:26]2[CH2:27][CH2:23][C:21]([O:20][CH2:18][CH3:19])=[O:22]

Participants

7

Reactant 4

HCID 119922-BromoanilineHCID 69136Ethyl 2-oxocyclopentanecarboxylateHCID 517045Sodium AcetateHCID 23668193Sodium Nitrite

Product 1

HCID 68940416ethyl 7-bromo-3-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent3×

Conditions

Temperature
19 °C

Procedure

A mixture of 2-bromoaniline (34.2 g) in 5M HCl (50 mL) and water (250 mL) at 0° C. was treated with NaNO2 (13.8 g) in water (200 mL). After addition, sodium acetate (92.3 g) in water (250 mL) and 2-oxo-cyclopentanecarboxylic acid ethyl ester (30 mL) were added. The mixture was stirred for 15 minutes, warmed to 19° C. over two hours and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The concentrate was dissolved in 1.1:1 H2SO4:ethanol (30 mL), refluxed overnight, cooled to room temperature, quenched with water (1.5 L), and filtered. The filtrant was dissolved in dichloromethane (200 mL) and filtered through a Flash 75 cartridge with dichloromethane. After concentration, the product was recrystallized from hexane.

Workup

  1. additionwere added
  2. extractionextracted with dichloromethane
  3. dry with materialThe extract was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe concentrate was dissolved in 1.1:1 H2SO4
  7. temperatureethanol (30 mL), refluxed overnight
  8. temperaturecooled to room temperature
  9. customquenched with water (1.5 L)
  10. filtrationfiltered
  11. dissolutionThe filtrant was dissolved in dichloromethane (200 mL)
  12. filtrationfiltered through a Flash 75 cartridge with dichloromethane
  13. concentrationAfter concentration
  14. customthe product was recrystallized from hexane

Sources & evidence

ORD record
ord-7892fadc0e244a84b8a6dfa413337b8e
Source dataset
uspto-grants-2015_05
Patent number
US09035047B2

Reaction notes

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