Ethyl formate → 1-Cyclopropyl-6-fluoro-7-(4-formyl-3-methyl-1-piperazinyl)-5-methyl-4-oxo-3-formyl1,2,3,4-tetrahydroquinoline

HRID 1073760Notes

Reaction equation

HRID 1073760 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH3:22])[C:10]([F:21])=[C:11]([N:14]4[CH2:19][CH2:18][NH:17][CH:16]([CH3:20])[CH2:15]4)[CH:12]=3)[C:7](=[O:23])[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[CH3:24][O-:25].[Na+].[CH:27](OCC)=[O:28]>ClCCl>[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH3:22])[C:10]([F:21])=[C:11]([N:14]4[CH2:19][CH2:18][N:17]([CH:27]=[O:28])[CH:16]([CH3:20])[CH2:15]4)[CH:12]=3)[C:7](=[O:23])[CH:6]([CH:24]=[O:25])[CH2:5]2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 8025Ethyl formateHCID 10942334Sodium MethoxideHCID 157127231-Cyclopropyl-6-fluoro-7-(3-methyl-1-piperazinyl)5-methyl-4-oxo-1,2,3,4-tetrahydroquinoline

Product 1

HCID 157127251-Cyclopropyl-6-fluoro-7-(4-formyl-3-methyl-1-piperazinyl)-5-methyl-4-oxo-3-formyl1,2,3,4-tetrahydroquinolineYield 65.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Cyclopropyl-6-fluoro-7-(3-methyl-1-piperazinyl)5-methyl-4-oxo-1,2,3,4-tetrahydroquinoline (5.7 g) is dissolved in dichloromethane (200 ml) and thereto is added gradually sodium methylate (6.8 g) and further added dropwise a solution of ethyl formate (9.3 g) in dichloromethane (100 ml). The mixture is stirred at room temperature for one hour and then refluxed for one hour. After cooling, the reaction mixture is washed with water (200 ml) and dilute aqueous sodium hydroxide solution (200 ml) and extracted. The aqueous layer is taken and is made weakly acidic with diluted hydrochloric acid and extracted with dichloromethane. The extract is washed with water, dried and then dichloromethane is distilled off. The resulting residue is purified by silica gel column chromatography (eluent, chloroform) and recrystallized from diethyl ether - isopropanol to give 1-cyclopropyl-6-fluoro-7-(4-formyl-3-methyl-1-piperazinyl)-5-methyl-4-oxo-3-formyl1,2,3,4-tetrahydroquinoline (4.4 g) as yellow powdery crystals, m.p. 148°-150° C.

Workup

  1. temperaturerefluxed for one hour
  2. temperatureAfter cooling
  3. washthe reaction mixture is washed with water (200 ml) and dilute aqueous sodium hydroxide solution (200 ml)
  4. extractionextracted
  5. extractionextracted with dichloromethane
  6. washThe extract is washed with water
  7. customdried
  8. distillationdichloromethane is distilled off
  9. customThe resulting residue is purified by silica gel column chromatography (eluent, chloroform)
  10. customrecrystallized from diethyl ether - isopropanol

Sources & evidence

ORD record
ord-db1329f4e4fa437faccb6f58cc25cfeb
Source dataset
uspto-grants-1990_11
Patent number
US04971970

Reaction notes

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