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

HRID 492208Notes

Reaction equation

HRID 492208 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]([O:15][CH3:16])=[O:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1.Cl[C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[CH:20][CH:19]=1.O>CN(C)C=O>[F:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]([O:15][CH3:16])=[O:14])=[CH:9][N:10]2[C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 691404-ChloroquinolineHCID 34176454Methyl 6-fluoro-1H-indole-3-carboxylate

Product 1

HCID 68971643Methyl 6-fluoro-1-(quinolin-4-yl)-1H-indole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

0.25 g (7.8 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 1.5 g (7.76 mmol) of 6-fluoro-3-methoxycarbonyl-1H-indole in 40 cm3 of dimethylformamide. After stirring at a temperature in the region of 40° C. for 0.5 hour, 1.29 g (7.8 mmol) of 4-chloroquinoline are added. After stirring at a temperature in the region of 120° C. for 6 hours, the reaction mixture is poured into 150 cm3 of water and extracted with 150 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 a brown solid which is purified by silica gel chromatography [eluent: dichloromethane and then dichloromethane/ethyl acetate (90/10 by volume)]. After concentrating the fractions under reduced pressure, 1.5 g of 6-fluoro-3-methoxycarbonyl-1-(quinol-4-yl)-1H-indole are obtained in the form of a beige-coloured solid melting at 186° C.

Workup

  1. stirringAfter stirring at a temperature in the region of 120° C. for 6 hours
  2. extractionextracted with 150 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)
  7. customto give a brown solid which
  8. customis purified by silica gel chromatography [eluent
  9. concentrationAfter concentrating the fractions under reduced pressure, 1.5 g of 6-fluoro-3-methoxycarbonyl-1-(quinol-4-yl)-1H-indole

Sources & evidence

ORD record
ord-f69717b1bbc94a09abb1a459a32f4a00
Source dataset
uspto-grants-2009_05
Patent number
US07531663B2

Reaction notes

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