Water → Methyl 5-fluoro-1-(quinolin-4-yl)-1H-indole-3-carboxylate

HRID 492212Notes

Reaction equation

HRID 492212 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]([O:15][CH3:16])=[O:14].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:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:18]1[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=1)[CH:8]=[C:7]2[C:13]([O:15][CH3:16])=[O:14]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 691404-ChloroquinolineHCID 34176452Methyl 5-fluoro-1H-indole-3-carboxylate

Product 1

HCID 68968517Methyl 5-fluoro-1-(quinolin-4-yl)-1H-indole-3-carboxylateYield 93.4%

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 2.26 g.(11.7 mmol) of 5-fluoro-3-methoxycarbonyl-1H-indole in 60 cm3 of dimethylformamide. After stirring at a temperature in the region of 40° C. for 0.5 hour, 1.98 g (12 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 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 3.5 g of a brown solid which is purified by silica gel chromatography (eluent: dichloromethane). After concentrating the fractions under reduced pressure, 1.6 g of 5-fluoro-3-methoxycarbonyl-1-(quinol-4-yl)-1H-indole are obtained in the form of a beige-coloured solid melting at 172° C.

Workup

  1. stirringAfter stirring at a temperature in the region of 120° C. for 6 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-e02dbb61c72b44fbb5d8897cb4dbe869
Source dataset
uspto-grants-2009_05
Patent number
US07531663B2

Reaction notes

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