Potassium Carbonate → 4-(4-Chloro-2-methoxybenzyl)-2,5-difluoro-N-(methylsulfonyl)benzamide

HRID 2359270Notes

Reaction equation

HRID 2359270 reaction equation
Br[CH2:2][C:3]1[C:15]([F:16])=[CH:14][C:6]([C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8])=[C:5]([F:17])[CH:4]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[C:21]([O:28][CH3:29])[CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:2][C:3]2[C:15]([F:16])=[CH:14][C:6]([C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8])=[C:5]([F:17])[CH:4]=2)=[C:21]([O:28][CH3:29])[CH:20]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 3858606(4-Chloro-2-methoxyphenyl)boronic acidHCID 666671114-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide

Product 1

HCID 565927884-(4-Chloro-2-methoxybenzyl)-2,5-difluoro-N-(methylsulfonyl)benzamideYield 36.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide (Preparation 164, 100 mg, 0.27 mmol), (4-chloro-2-methoxyphenyl)boronic acid (55 mg, 0.295 mmol), tetrakis(triphenylphosphine)palladium (31 mg, 0.027 mmol), aqueous potassium carbonate solution (1.8 M, 0.45 mL, 0.804 mmol) and tetrahydrofuran (15 mL) were combined and stirred under nitrogen at reflux for 6 hours. After cooling, the mixture was filtered through Celite™ and the filtrate evaporated. The residue was dissolved in water (20 mL) and acidified with aqueous potassium hydrogen sulphate solution (0.5 M) to pH 2 and the mixture extracted with ethyl acetate (1×30 mL). The organic layer was separated and back-washed with brine (2×20 mL). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to give an orange oil. The oil was purified using silica gel column chromatography eluting with heptane to ethyl acetate:heptane 1:1 to give a solid. The solid was further purified by reverse phase HPLC to give the title compound (38 mg, 36%) as a white solid.

Workup

  1. temperatureat reflux for 6 hours
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered through Celite™
  4. customthe filtrate evaporated
  5. dissolutionThe residue was dissolved in water (20 mL)
  6. extractionthe mixture extracted with ethyl acetate (1×30 mL)
  7. customThe organic layer was separated
  8. washback-washed with brine (2×20 mL)
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltered
  12. customevaporated
  13. customto give an orange oil
  14. customThe oil was purified
  15. washeluting with heptane to ethyl acetate:heptane 1:1
  16. customto give a solid
  17. customThe solid was further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-8485b2cf49c54e7db93e059b711857ac
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

Loading…