Ethanol → Ethyl 5-methoxy-4,5,7-trimethylindole-2-carboxylate

HRID 2395741Notes

Reaction equation

HRID 2395741 reaction equation
N([O-])=O.[Na+].[CH3:5][C:6]1[C:12](C)=[C:11]([O:14][CH3:15])[C:10]([CH3:16])=[CH:9][C:7]=1[NH2:8].CC[C:19](=O)[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].[OH-].[K+].[CH2:29](O)C>O.Cl>[CH3:15][O:14][C:11]1([CH3:29])[CH:12]=[C:6]([CH3:5])[C:7]2[C:9]([CH:19]=[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:8]=2)=[C:10]1[CH3:16]

Participants

8

Reactant 5

HCID 702Ethanol3×HCID 14797Potassium HydroxideHCID 78656Ethyl 3-oxovalerateHCID 147002344-Methoxy-2,3,5-trimethylanilineHCID 23668193Sodium Nitrite

Product 1

HCID 19418845Ethyl 5-methoxy-4,5,7-trimethylindole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent3×HCID 962WaterSolvent2×

Procedure

A solution of sodium nitrite (1.91 g) in water (4.4 ml) is added (below the surface) to a cold (-10°) thick slurry of 2,3,5-trimethyl-4-methoxyaniline [J. Amer. Chem. Soc., 70 2656 (1948)] in ethanol (10 ml), water (54 ml) and concentrated hydrochloric acid (9.3 ml). The mixture is stirred for 30 min as the temperature rises to -1°, then the solution of the diazonium salt is poured into a vigorously stirred mixture of ethyl methylacetoacetate (3.68 g) in ethanol (24 ml) containing potassium hydroxide (45%), 6 ml) and ice (40 g). The mixture is allowed to warm to 20°-25° with continued stirring for 1 hr, then is extracted with toluene. The toluene extracts are dried (potassium carbonate) and concentrated to give an oil. A solution of the oil in ethanol (20 ml) is stirred while hydrogen chloride rapidly with an exotherm to 60°. The mixture is cooled and saturated with hydrogen chloride at 45°, then is stored overnight at 5°. The precipitate is collected and washed several times with cold ethanol. The solid is partitioned between ethyl acetate and aqueous bicarbonate, the phases separated, the organic phases dried and concentrated. The concentrate is crystallized from acetone/hexane to give the title compound, mp 182°-183°.

Workup

  1. customrises to -1°
  2. temperatureto warm to 20°-25°
  3. stirringwith continued stirring for 1 hr
  4. extractionis extracted with toluene
  5. dry with materialThe toluene extracts are dried (potassium carbonate)
  6. concentrationconcentrated
  7. customto give an oil
  8. waitis stored overnight at 5°
  9. customThe precipitate is collected
  10. washwashed several times with cold ethanol
  11. customThe solid is partitioned between ethyl acetate and aqueous bicarbonate
  12. customthe phases separated
  13. customthe organic phases dried
  14. concentrationconcentrated
  15. customThe concentrate is crystallized from acetone/hexane

Sources & evidence

ORD record
ord-4ac7a82c7a5b40d6ad6fe8e1f69dd781
Source dataset
uspto-grants-1996_02
Patent number
US05489593

Reaction notes

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