Tetrafluoroboric acid → 5-Chloro-4-hydroxy-2-methoxybenzoic acid

HRID 630396Notes

Reaction equation

N[C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.F[B-](F)(F)F.[H+].N([O-])=[O:21].[Na+]>O>[Cl:11][C:10]1[C:2]([OH:21])=[CH:3][C:4]([O:12][CH3:13])=[C:5]([CH:9]=1)[C:6]([OH:8])=[O:7]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of 4-amino-5-chloro-2-methoxybenzoic acid (25 g; 0.12 mol) in 125 ml of water was added tetrafluoroboric acid (40.5 ml of 48% aqueous solution). The white cake was then cooled to 0° C. and NaNO2 (9.41 g in 75 mL of H2O) was added drop wise and the whole stirred at that temperature for 30 minutes. The white precipitate was collected by filtration. The diazonium salt was suspended in glacial AcOH (1250 mL) and the resulting suspension was stirred at 100° C. for 1 hour (it became a brown solution). It was allowed to stand at RT for two more hours. The solvent was removed under reduced pressure and the brown oily residue suspended in brine (1250 ml) and extracted with EtOAC (3×400 ml). The combined organic layers were dried over magnesium sulphate, filtered and evaporated under reduced pressure to give brown oil. Purification by preparative reversed-phase HPLC (Et2O/EtOH 0/100 to 40/60) afforded 3.0 g (13%) of a red solid.

Workup

filtrationThe white precipitate was collected by filtration
stirringthe resulting suspension was stirred at 100° C. for 1 hour (it
customto stand at RT for two more hours
customThe solvent was removed under reduced pressure
extractionextracted with EtOAC (3×400 ml)
dry with materialThe combined organic layers were dried over magnesium sulphate
filtrationfiltered
customevaporated under reduced pressure
customto give brown oil
customPurification by preparative reversed-phase HPLC (Et2O/EtOH 0/100 to 40/60)

Sources & evidence

ORD record: ord-025c710a41e1450da87c5dac9a85e744
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315463B2

Reaction notes

Loading…