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

HRID 1404776Notes

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

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 11 g, 25%) as a brown solid, 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ12.72 (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

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

Sources & evidence

ORD record: ord-48f356e5599b412190443986205652e4
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912331B2

Reaction notes

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