Water → Methyl 6-methoxy-1-(quinolin-4-yl)-1H-indole-3-carboxylate

HRID 492205Notes

Reaction equation

HRID 492205 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][NH:11]2)=[CH:7][CH:6]=1.Cl[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[CH:21][CH:20]=1.O>CN(C)C=O>[CH3:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][N:11]2[C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[CH:21][CH:20]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 691404-ChloroquinolineHCID 14787876Methyl 6-methoxy-1H-indole-3-carboxylate

Product 1

HCID 68970361Methyl 6-methoxy-1-(quinolin-4-yl)-1H-indole-3-carboxylateYield 100.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

0.384 g (12 mmol) of sodium hydride, at 75% by mass in liquid petroleum jelly, is added at a temperature in the region of 20° C. under an argon atmosphere to a solution of 2.4 g (11.7 mmol) of 6-methoxy-3-methoxycarbonyl-1H-indole in 60 cm3 of dimethylformamide. After stirring at a temperature in the region of 40° C. for 0.3 hours, 1.98 g (12 mmol) of 4-chloroquinoline are added. After stirring at a temperature in the region of 120° C. for 5 hours, the reaction mixture is poured into 200 cm3 of water and extracted with 200 cm3 of ethyl acetate. The organic phase is washed with 3 times 100 cm3 of water and is then dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) to give 3.9 g of a brown residue which is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate (65/35 by volume)]. After concentrating the fractions under reduced pressure, 2.5 g of 6-methoxy-3-methoxycarbonyl-1-(quinol-4-yl)-1H-indole are obtained in the form of a beige-coloured solid melting at 162° C.

Workup

  1. stirringAfter stirring at a temperature in the region of 120° C. for 5 hours
  2. extractionextracted with 200 cm3 of ethyl acetate
  3. washThe organic phase is washed with 3 times 100 cm3 of water
  4. dry with materialis then dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-c67deaac658d4e6d86884e234c6677d4
Source dataset
uspto-grants-2009_05
Patent number
US07531663B2

Reaction notes

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