Pyridine → 4-Chloro-5,6,7,8-tetrahydrocinnoline-3-carboxylic acid ethyl ester

HRID 567703Notes

Reaction equation

HRID 567703 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=O)[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[NH:8][N:7]=1)=[O:5])[CH3:2].[Cl-].[Li+].N1C=CC=CC=1.C1(C)C=CC(S([Cl:34])(=O)=O)=CC=1>ClCCl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[N:8][C:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=2[C:15]=1[Cl:34])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 1049PyridineHCID 73974-Toluenesulfonyl chlorideHCID 433294Lithium ChlorideHCID 541078584-Oxo-1,4,5,6,7,8-hexahydrocinnoline-3-carboxylic acid ethyl ester

Product 1

HCID 538971714-Chloro-5,6,7,8-tetrahydrocinnoline-3-carboxylic acid ethyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of 4-oxo-1,4,5,6,7,8-hexahydrocinnoline-3-carboxylic acid ethyl ester (1 g), lithium chloride (0.19 g) and pyridine (0.36 ml) in dichloromethane (30 ml) was added p-toluenesulphonyl chloride (0.85 g). The reaction mixture was heated at reflux for 20 h. The solid was collected by filtration, and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography using a gradient elution: CH2Cl2 (500 ml), CH2Cl2/MeOH 99:1 (500 ml), CH2Cl2/MeOH 98:2 (1 liter). The appropriate fractions were combined and evaporated under reduced pressure to give a solid (0.65 g, 61%). δH (360 MHz; CDCl3) 1.44 (3H, t, J=7 Hz, CH3), 1.89 (4H, m, CH2), 2.85 (2H, t, J=5.7 Hz, CH2), 2.62 (2H, t, J=5.7 Hz, CH2), 4.51 (2H, t, J=7 Hz, CH2), m/z (ESP+) 241/243 (MH+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 20 h
  3. filtrationThe solid was collected by filtration
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by flash chromatography
  6. washa gradient elution
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5ee0ebb9e7144e0ab1c7d1276273d512
Source dataset
uspto-grants-2001_01
Patent number
US06180630B2

Reaction notes

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