Sulfuric Acid → HCID 67382994, compound

HRID 335911Notes

Reaction equation

HRID 335911 reaction equation
[Br:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:8]=2[C:9]([OH:11])=O)=[CH:4][C:3]=1[F:20].S(=O)(=O)(O)O.BrC1C=CC2OC3C(=CC(OC)=CC=3)C(=O)C=2C=1F>>[Br:1][C:2]1[C:3]([F:20])=[CH:4][C:5]2[O:6][C:7]3[C:8](=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=3)[C:9](=[O:11])[C:18]=2[CH:19]=1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 67383149HCID 67383149, compoundHCID 67383584HCID 67383584, compound

Product 1

HCID 67382994HCID 67382994, compoundYield 42.3%

Conditions

Temperature
80 °C

Procedure

To a 1 L flask charged with 2-(4-bromo-3-fluorophenoxy)-5-methoxybenzoic acid (100 g, 293 mmol) was added sulfuric acid (391 mL, 7329 mmol). The resulting slurry was heated to 80° C. for 2 hours. The reaction was removed from the oil bath, cooled to rt and poured into a 3 L flask containing 2 L of ice water. The derived slurry was vigorously stirred for 2 hours before being filtered. The derived solid was washed well with water (3×500 mL), 3 N NaOH (2×500 mL) and water (2×500 mL). The wet solid was then washed with ether (2×250 mL) and dried under a vacuum at 50° C. overnight. The solid was then azeotropped from toluene (3×100 mL) to provide 41 g of a 4:1 mixture of 2-bromo-1-fluoro-7-methoxy-9H-xanthen-9-one:2-bromo-3-fluoro-7-methoxy-9H-xanthen-9-one (40.0 g, 123.9 mmol, 42.2% yield). A portion of this material (10 g) was slurried in hot IPA (200 mL) and placed in the refrigerator overnight. The derived solid was filtered and purified by silica gel chromatography (100% CH2Cl2) to provide 2-bromo-1-fluoro-7-methoxy-9H-xanthen-9-one (4.1 g) and 2-bromo-3-fluoro-7-methoxy-9H-xanthen-9-one (0.95 g) both as light white solids.

Workup

  1. customThe reaction was removed from the oil bath
  2. temperaturecooled to rt
  3. additionpoured into a 3 L flask
  4. additioncontaining 2 L of ice water
  5. filtrationbefore being filtered
  6. washThe derived solid was washed well with water (3×500 mL), 3 N NaOH (2×500 mL) and water (2×500 mL)
  7. washThe wet solid was then washed with ether (2×250 mL)
  8. customdried under a vacuum at 50° C. overnight
  9. customto provide

Sources & evidence

ORD record
ord-f030ce1177704cf3a057799feea7c10d
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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