Trifluoroacetic acid → 7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-one

HRID 1855297Notes

Reaction equation

HRID 1855297 reaction equation
[Br:1][C:2]1[CH:3]=[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.C(O)(C(F)(F)F)=O.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.B(F)(F)F.CCOCC>O>[Br:1][C:2]1[CH:10]=[C:6]2[C:5]([O:11][C:12]3[C:13]([F:20])=[CH:14][C:15]([O:18][CH3:19])=[CH:16][C:17]=3[C:7]2=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8000Boron trifluoride etherateHCID 9845Trifluoroacetic anhydrideHCID 574756385-Bromo-2-(2-fluoro-4-methoxyphenoxy)benzoic acid

Product 1

HCID 574756397-bromo-4-fluoro-2-methoxy-9H-xanthen-9-oneYield 58.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A dry 100 L glass jacketed reactor equipped with an addition funnel, reflux condenser and temperature probe was charged with 5-bromo-2-(2-fluoro-4-methoxyphenoxy)benzoic acid (2340 g, 6.9 mol). TFA (11.7 L) was carefully added to the mixture followed by TFAA (1144 mL). Boron trifluoride diethyl etherate (85 mL, 0.68 mol) was then carefully added, and the mixture was stirred for 4 hours at which point the reaction was transferred to another 100 L glass reactor containing 35.1 L of water cooled at 0° C. The resulting slurry was allowed to warm to RT and stirred for 1 hour. The solids were filtered and washed with water (4.7 L) and 3 N NaOH (2×3.5 L) and water (7 L). The solids were transferred into a 22 L reactor and acetone (4.7 L) was added. The solids were slurried for 1.5 hour and the filtered, washing well with acetone (4.7 L). An additional slurry with acetone (6.4 L @ 45° C.) provided 1310 g of 7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-one as an off white solid.

Workup

  1. customequipped with an addition funnel
  2. temperaturereflux condenser
  3. customwas transferred to another 100 L glass reactor
  4. temperatureto warm to RT
  5. stirringstirred for 1 hour
  6. filtrationThe solids were filtered
  7. washwashed with water (4.7 L) and 3 N NaOH (2×3.5 L) and water (7 L)
  8. customThe solids were transferred into a 22 L reactor
  9. additionacetone (4.7 L) was added
  10. waitThe solids were slurried for 1.5 hour
  11. washthe filtered, washing well with acetone (4.7 L)

Sources & evidence

ORD record
ord-e99afb37e35e46b9b6d29d0abc85366c
Source dataset
uspto-grants-2015_02
Patent number
US08962859B2

Reaction notes

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