Hydrochloric Acid → 2-(5,7-Difluoroquinolin-6-yl)acetic acid

HRID 449257Notes

Reaction equation

HRID 449257 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([CH2:9][C:10]([OH:12])=[O:11])=[C:4]([F:13])[CH:3]=1.[N+]([C:17]1[CH:22]=CC=C[CH:18]=1)([O-])=O.OS(O)(=O)=O.[OH-].[Na+].Cl>OCC(CO)O.CO>[F:13][C:4]1[C:5]([CH2:9][C:10]([OH:12])=[O:11])=[C:6]([F:8])[CH:7]=[C:2]2[C:3]=1[CH:18]=[CH:17][CH:22]=[N:1]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 7416NitrobenzeneHCID 14798Sodium HydroxideHCID 552533832-(4-Amino-2,6-difluorophenyl)acetic acid

Product 1

HCID 577423352-(5,7-Difluoroquinolin-6-yl)acetic acidYield 43.7%

Reagents, catalysts & solvents 2

HCID 753GlycerolSolventHCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-amino-2,6-difluorophenylacetic acid (3.2 g, 17.1 mmol), ferrous sulphate (1.04 g, 3.76 mmol), nitrobenzene (1.05 ml, 10.26 mmol) and conc. H2SO4 in glycerol (5.2 ml) was heated at 150° C. for 16 h. The mixture was cooled to RT, methanol (28 ml) was added followed by aq. 6N NaOH (28 ml) and heated at 110° C. for 3 h. After cooling to RT, the mixture was acidified with conc. HCl to pH 3.0. The precipitate formed was filtered, washed with water and dried under vacuum. The precipitate was refluxed with methanol, filtered under hot conditions and the filtrate was evaporated to give the title compound (1 g, 25%) as a brown solid. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 12.72 (bs, 1H), 8.98 (d, J=3.1 Hz, 1H); 8.47 (d, J=8.4, 1H); 7.71 (d, J=9.7, 1H); 7.62 (dd, J=8.4, 4.1, 2H); 3.85 (s, 2H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. temperatureheated at 110° C. for 3 h
  3. temperatureAfter cooling to RT
  4. customThe precipitate formed
  5. filtrationwas filtered
  6. washwashed with water
  7. customdried under vacuum
  8. temperatureThe precipitate was refluxed with methanol
  9. filtrationfiltered under hot conditions
  10. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-10274d29d4214ad4bc631dd16f635129
Source dataset
uspto-grants-2013_07
Patent number
US08481739B2

Reaction notes

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