Acetamidomalonic acid diethyl ester → Diethyl (6-methoxy-3-quinolyl)methylacetamidomalonate

HRID 1090007Notes

Reaction equation

HRID 1090007 reaction equation
[O-]CC.[Na+].[Na].[C:6]([NH:9][CH:10]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])(=[O:8])[CH3:7].Cl.Cl[CH2:23][C:24]1[CH:25]=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([O:34][CH3:35])=[CH:29][CH:28]=2>C(O)C>[CH3:35][O:34][C:30]1[CH:31]=[C:32]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]([CH2:23][CH2:7][C:6]([NH:9][CH:10]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:8])=[CH:33]2

Participants

6

Reactant 4

HCID 14041Acetamidomalonic acid diethyl esterHCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 190420403-Chloromethyl-6-methoxyquinoline hydrochloride

Product 1

HCID 57184951Diethyl (6-methoxy-3-quinolyl)methylacetamidomalonateYield 75.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of sodium ethoxide prepared from 0.3 g (13.1 mmol) of sodium and 30 mL of ethanol were added, in one portion, 2.85 g (13.1 mmol) of diethyl acetamidomalonate. After 30 minutes, 1.52 g (6.24 mmol) of 3-chloromethyl-6-methoxyquinoline hydrochloride were added and the resultant mixture was refluxed overnight. The reaction mixture was evaporated and the residue was dissolved in 25 mL of 1N hydrochloric acid and extracted twice with ethyl ether. The aqueous layer was neutralized with solid sodium bicarbonate and extracted twice with chloroform. The chloroform layer was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel, using first 4:1 methylene chloride/ethyl acetate and then 1:1 methylene chloride/ethyl acetate as eluents, to give 1.82 g (75.2%) of the desired product as a white solid, which melted at 151°-152° C. after crystallization from a mixture of ethyl acetate and isopropyl ether. TLC Rf =0.34 (ethyl acetate); NMR (CDCl3) δ 8.4 (1H, d), 7.9 (1H, d), 7.7 (1H, bs), 7.35 (1H, d), 7.0 (1H, d), 6.6 (1H, bs), 4.3 (4H, q), 3.9 (3H, s), 3.85 (2H, s), 2.05 (3H, s), 1.3 (6H, t); IR (KBr) ν 3400, 3230, 1740, 1640, 1300 cm-1. The product has the formula: ##STR104##

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionthe residue was dissolved in 25 mL of 1N hydrochloric acid
  3. extractionextracted twice with ethyl ether
  4. extractionextracted twice with chloroform
  5. washThe chloroform layer was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-54c7c6782b9c4ef5bdb4c3a8a3171147
Source dataset
uspto-grants-1992_01
Patent number
US05079366

Reaction notes

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