5-Bromo-4-fluoro-2-(2-fluoro-4-methoxyphenoxy)benzoic acid → 2-bromo-3,5-difluoro-7-methoxy-9H-xanthen-9-one

HRID 335909Notes

Reaction equation

[Br:1][C:2]1[C:3]([F:21])=[CH:4][C:5]([O:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=2[F:20])=[C:6]([CH:10]=1)[C:7]([OH:9])=O>CCOC(C)=O>[Br:1][C:2]1[C:3]([F:21])=[CH:4][C:5]2[O:11][C:12]3[C:17](=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[F:20])[C:7](=[O:9])[C:6]=2[CH:10]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a flaske charged with polyphosphoric acid (396 g, 4038 mmol) was added 5-bromo-4-fluoro-2-(2-fluoro-4-methoxyphenoxy)benzoic acid (58 g, 162 mmol) and the viscous mixture was heated at 140° C. for 2 hours. The viscous solution was cooled slightly and diluted with ice-water (1 L). After 15 min of stirring, EtOAc (1 L) was added and the aqueous fraction extracted with EtOAc (3×200 mL). The combined organic fractions were dried over sodium sulfate and concentrated. The solids were washed with 6 N NaOH, then water. The solids were then sequentially triturated with methanol and ethyl acetate. The resulting solid was dried under vacuum to afford 2-bromo-3,5-difluoro-7-methoxy-9H-xanthen-9-one (41 g, 120 mmol, 74.4% yield).

Workup

temperatureThe viscous solution was cooled slightly
extractionthe aqueous fraction extracted with EtOAc (3×200 mL)
dry with materialThe combined organic fractions were dried over sodium sulfate
concentrationconcentrated
washThe solids were washed with 6 N NaOH
customThe solids were then sequentially triturated with methanol and ethyl acetate
customThe resulting solid was dried under vacuum

Sources & evidence

ORD record: ord-880c182dcd414f398c14dcbc2d30942b
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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