HCID 10979076, compound → HCID 14835484, compound

HRID 1708884Notes

Reaction equation

HRID 1708884 reaction equation
[Cl:1][C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:14])[CH2:5][CH:6]([CH3:13])[NH:7]2.[S:15]([N:25]1[CH2:32][CH2:31][CH2:30][C@H:26]1[C:27](Cl)=[O:28])([C:18]1[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=1)(=[O:17])=[O:16]>N1C=CC=CC=1.ClCCl>[Cl:1][C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:14])[CH2:5][CH:6]([CH3:13])[N:7]2[C:27](=[O:28])[C@@H:26]1[CH2:30][CH2:31][CH2:32][N:25]1[S:15]([C:18]1[CH:19]=[CH:20][C:21]([CH3:22])=[CH:23][CH:24]=1)(=[O:17])=[O:16]

Participants

5

Reactant 2

HCID 10979076HCID 10979076, compoundHCID 13960198HCID 13960198, compound

Product 1

HCID 14835484HCID 14835484, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

36.7g of (+)-5-chloro-6-fluoro-2-methyl-4-oxo1,2,3,4-tetrahydroquinoline was dissolved in 34.3 g of pyridine and 400 ml of dichloromethane. Then, a solution of N-tosyl-L-prolyl chloride (prepared from 92.4 g of N-tosyl-L-proline and 74.5 ml of thionyl chloride) in 70 ml of dichloromethane was added thereto at room temperature over a period of 20 minutes. After completion of the addition, the resulting mixture was stirred for 15 minutes and then heated under reflux for 20 minutes. This reaction mixture was allowed to cool, washed successively with dilute hydrochloric acid, an aqueous solution of sodium hydrogen carbonate and water, and then dried. Thereafter, the solvent was evaporated under reduced pressure to obtain a residue comprising a mixture diastereomers of 5-chloro-6-fluoro-2-methyl-4-oxo-1-(N-tosyl-L prolyl)-1,2,3,4-tetrahydroquinoline. This residue was subjected to silica gel column chromatography using chloroform-ethyl acetate (10:1) as the eluent, and then subjected to thin-layer chromatography [using chloroform-ethyl acetate (10:1) as the developing solvent]. Fractions having an Rf value of 0.47 were collected and concentrated under reduced pressure to obtain 36.8 g of (+)-5-chloro-6-fluoro-2-methyl-4-oxo-1-(N-tosyl-L-prolyl)-1,2,3,4-tetrahydroquinoline.

Workup

  1. additionAfter completion of the addition
  2. temperatureheated
  3. temperatureunder reflux for 20 minutes
  4. temperatureto cool
  5. washwashed successively with dilute hydrochloric acid
  6. dry with materialan aqueous solution of sodium hydrogen carbonate and water, and then dried
  7. customThereafter, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4cc784448d7c49b08a510cbc4755c5fb
Source dataset
uspto-grants-1990_08
Patent number
US04946844

Reaction notes

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