Sodium Hydroxide → HCID 9801173, compound

HRID 2293601Notes

Reaction equation

HRID 2293601 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[C:18]([O:20]CC)=[O:19])=[CH:5][CH:4]=1.[CH3:23][O:24][C:25]1[CH:40]=[CH:39][C:28]([CH2:29]C(C(=O)C)C(OCC)=O)=[CH:27][CH:26]=1.[OH-:41].[Na+].[Cl-].C1([N+]#N)C=CC=CC=1>CCOC(C)=O.O>[CH2:23]1[O:24][C:25]2[CH:40]=[CH:39][C:28]([CH2:29][N:11]3[C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)=[C:10]3[C:18]([OH:20])=[O:19])=[CH:27][C:26]=2[O:41]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 60992Benzenediazonium chlorideHCID 12248936Ethyl α-acetyl-4-methoxybenzenepropanoateHCID 22676729HCID 22676729, compound

Product 1

HCID 9801173HCID 9801173, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 3-(4-methoxyphenyl)indole-2-carboxylate. To a solution of ethyl 2-(4-methoxybenzyl)-3-oxobutyrate (1.0 g, 4 mmol) in EtOAc (6 mL) stirred at ice bath temperature under an argon atmosphere was added a solution of NaOH (0.48 g, 12 mmol) in H2O (2 mL). This was immediately followed by the addition of an aqueous solution of benzenediazonium chloride (4.2 mmol) [prepared from aniline, (0.39 g, 4.2 mmol) in 6N HCl (0.5 mL) and NaNO2 (0.29 g, 4.2 mmol)]. After 10 min the mixture was partitioned between EtOAc (50 mL) and H2O (25 mL). The aqueous layer was washed with EtOAc (15 mL). The combined organic extracts were washed with saturated aqueous NaCl solution, dried (Na2SO4) and the solvent was removed in vacuo. The residue was dissolved in EtOH (10 mL) and the solution was saturated with HCl gas. This was refluxed for 1 h then cooled to room temperature and partitioned EtOAc (50 mL) and saturated aqueous NaHCO3 solution (50 mL). The aqueous layer was washed with EtOAc (15 mL). The combined organic extract was washed with H2O then saturated aqueous NaCl solution, dried (Na2SO4) and the solvent was removed in vacuo. Chromatography (silica gel, gradient elution from 25% Et2O/hexanes to 45% Et2O/hexanes) followed by crystallization from EtOAc/hexanes to afford the title compound (0.32 g, 27%); m.p. 109°-111° C.

Workup

  1. customAfter 10 min the mixture was partitioned between EtOAc (50 mL) and H2O (25 mL)
  2. washThe aqueous layer was washed with EtOAc (15 mL)
  3. washThe combined organic extracts were washed with saturated aqueous NaCl solution
  4. dry with materialdried (Na2SO4)
  5. customthe solvent was removed in vacuo
  6. dissolutionThe residue was dissolved in EtOH (10 mL)
  7. temperatureThis was refluxed for 1 h
  8. custompartitioned EtOAc (50 mL) and saturated aqueous NaHCO3 solution (50 mL)
  9. washThe aqueous layer was washed with EtOAc (15 mL)
  10. extractionThe combined organic extract
  11. washwas washed with H2O
  12. dry with materialsaturated aqueous NaCl solution, dried (Na2SO4)
  13. customthe solvent was removed in vacuo
  14. washChromatography (silica gel, gradient elution from 25% Et2O/hexanes to 45% Et2O/hexanes)
  15. customfollowed by crystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-bf5770612a8c42c1bde9b35510f0577a
Source dataset
uspto-grants-1997_11
Patent number
US05686481

Reaction notes

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