4-Methoxybenzyl alcohol → 1-Ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

HRID 525942Notes

Reaction equation

HRID 525942 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2F)[C:6](=[O:16])[C:5]([C:17]([O:19]CC)=[O:18])=[CH:4]1)[CH3:2].[OH-:22].[K+].[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][OH:31])=[CH:28][CH:27]=1>>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([O:22][CH2:30][C:29]3[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[C:11]=2[O:31][CH2:30][C:29]2[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2]

Participants

4

Reactant 3

HCID 77384-Methoxybenzyl alcoholHCID 14797Potassium HydroxideHCID 5140913Ethyl 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate

Product 1

HCID 867328111-Ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acidYield 52.1%

Conditions

Temperature
75 °C

Procedure

A mixture of ethyl 1-ethyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (50 g, 167 mmol), KOH (94 g, 1671 mmol) and 4-methoxybenzyl alcohol (208 ml, 1671 mmol) was heated at 75° C. for 4 hours. LCMS showed completion of reaction. The solution was adjusted to pH 2 and was extracted with ethyl acetate. The organic layer was washed with water, dried with Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with ethyl acetate, whereupon the crude product precipitated out as a solid substance. The precipitate was collected by filtration and washed with EA to afford 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (44 g, 87 mmol, 51.9% yield) as a yellow solid. LCMS: (M+H)+: 508.3.

Workup

  1. customcompletion of reaction
  2. extractionwas extracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated with ethyl acetate, whereupon the crude product
  8. customprecipitated out as a solid substance
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with EA

Sources & evidence

ORD record
ord-e1070f4125d348f1926e8845e9e4c9ef
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

Loading…