Hydrochloric Acid → Methyl 3-cyclohexyl-1H-indole-6-carboxylate

HRID 1354504Notes

Reaction equation

HRID 1354504 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:19](=O)([O-])[O-].[K+].[K+].IC.Cl>O.CN(C=O)C>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 112419893-cyclohexyl-1H-indole-6-carboxylic Acid

Product 1

HCID 11230631Methyl 3-cyclohexyl-1H-indole-6-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 2 L flask equipped with a dropping funnel and mechanical stirrer was charged with crude 3-cyclohexyl-6-indole carboxylic acid (99.4 g, 0.409 mole) and anhydrous DMF (665 mL) was added followed by anhydrous potassium carbonate (78.13 g, 0.565 mole). Iodomethane (63.72 g, 0.449 mole) was added dropwise over 35 min with stirring to the slurry which was then stirred overnight at room temperature until complete disappearance of starting material (TLC). The resulting suspension was then poured into water (1350 mL) and acidified to pH 4 with 4N HCl (200 mL). The product was extracted into ether (3×1700 mL), washed with water and brine and dried (Na2SO4). Volatiles were removed under reduced pressure and the residue was triturated with hexane (700 mL). The beige solid was filtered and dried under vacuum (94.3 g, 90% yield).

Workup

  1. customA 2 L flask equipped with a dropping funnel and mechanical stirrer
  2. additionwas added
  3. stirringwas then stirred overnight at room temperature until complete disappearance of starting material (TLC)
  4. extractionThe product was extracted into ether (3×1700 mL)
  5. washwashed with water and brine
  6. dry with materialdried (Na2SO4)
  7. customVolatiles were removed under reduced pressure
  8. customthe residue was triturated with hexane (700 mL)
  9. filtrationThe beige solid was filtered
  10. customdried under vacuum (94.3 g, 90% yield)

Sources & evidence

ORD record
ord-dca88ee8984a4d549f79852e65a38719
Source dataset
uspto-grants-2007_05
Patent number
US07223785B2

Reaction notes

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