Hydrochloric Acid → 4-Fluoro-benzyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid ethyl ester

HRID 1767474Notes

Reaction equation

HRID 1767474 reaction equation
[C:1]([O:9]CC)(=O)[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[H][H].[F:16][C:17]1[CH:36]=[CH:35][C:20]([CH2:21][N:22]2[C:27]3[CH:28]=[CH:29][C:30]([CH3:32])=[CH:31][C:26]=3[C:25](=O)[O:24]C2=O)=[CH:19][CH:18]=1.Cl>CC(N(C)C)=O>[CH2:6]([O:5][C:3]([C:2]1[C:1](=[O:9])[N:22]([CH2:21][C:20]2[CH:35]=[CH:36][C:17]([F:16])=[CH:18][CH:19]=2)[C:27]2[C:26]([C:25]=1[OH:24])=[CH:31][C:30]([CH3:32])=[CH:29][CH:28]=2)=[O:4])[CH3:7]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 865946424-Fluorobenzyl-6-methyl-1H-benzo[d][1,3]oxazine-2,4-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 694780414-Fluoro-benzyl-4-hydroxy-6-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid ethyl esterYield 71.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
90 °C

Procedure

Neat diethyl malonate (3.04 mL, 20 mmol) was added slowly to a suspension of sodium hydride (60% in mineral oil, 0.88 g, 22 mmol) in dimethylacetamide under N2 atmosphere. The mixture was stirred at room temperature until the evolution of hydrogen gas ceased, then the mixture was heated to 90° C. for 30 min and cooled to room temperature. A solution of Compound 13 (6.3 g, 22 mmol) in dimethylacetamide was added slowly and the mixture heated overnight at 110° C. The mixture was cooled to room temperature, poured into ice water, and acidified by cold 10% HCl. The solids formed were filtered, washed several times by water, and dried at room temperature under vacuum to yield 5.1 g (71%) of white solids. M.P. 130° C. 1H NMR (DMSO-d6): δ 1.31 (t, J=7.0 Hz, 3H), 2.34 (s, 3H), 4.37 (q, J=7.5 Hz, 2H), 5.94 (s, 2H), 7.09–7.32 (m, 5H), 7.45 (dd, J=1.6, 8.7 Hz, 1H), 7.86 (d, J=1.5 Hz, 1H). EIMS m/z 356 (M+1), 378 (M+23). Anal. (C20H18FNO4) C, H, N.

Workup

  1. temperaturecooled to room temperature
  2. temperaturethe mixture heated overnight at 110° C
  3. temperatureThe mixture was cooled to room temperature
  4. customThe solids formed
  5. filtrationwere filtered
  6. washwashed several times by water
  7. customdried at room temperature under vacuum

Sources & evidence

ORD record
ord-96f8f2941d3e48e9882d759c526a0fb3
Source dataset
uspto-grants-2007_06
Patent number
US07235546B2

Reaction notes

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