Potassium Carbonate → 4-[4-chloro-3-(trifluoromethyl)phenoxy]-3,6-difluoro-2-methoxy-N-(methylsulfonyl)benzamide

HRID 2359263Notes

Reaction equation

HRID 2359263 reaction equation
[F:1][C:2]1[C:3]([O:12][CH3:13])=[C:4]([C:7]([F:11])=[CH:8][C:9]=1F)[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][C:22]=1[C:28]([F:31])([F:30])[F:29].[CH3:32][S:33]([NH2:36])(=[O:35])=[O:34].C(C(OC1C(OC(C(C)(C)C)=O)=C(I)C=CC=1)=O)(C)(C)C>CS(C)=O.C(OCC)(=O)C.[Rh]>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:9]2[CH:8]=[C:7]([F:11])[C:4]([C:5]([NH:36][S:33]([CH3:32])(=[O:35])=[O:34])=[O:6])=[C:3]([O:12][CH3:13])[C:2]=2[F:1])=[CH:23][C:22]=1[C:28]([F:29])([F:30])[F:31]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 72879MethanesulfonamideHCID 805204-Chloro-3-(trifluoromethyl)phenolHCID 534311013-Iodo-1,2-phenylene bis(2,2-dimethylpropanoate)HCID 580424893,4,6-Trifluoro-2-methoxybenzaldehyde

Product 1

HCID 565925314-[4-chloro-3-(trifluoromethyl)phenoxy]-3,6-difluoro-2-methoxy-N-(methylsulfonyl)benzamideYield 22.8%

Reagents, catalysts & solvents 3

HCID 23948RhodiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3,4,6-trifluoro-2-methoxybenzaldehyde (Preparation 29, 0.118 g, 0.000280 mol) and potassium carbonate (0.097 g, 0.000702 mol) in dimethyl sulfoxide (3.5 mL) was added 4-chloro-3-(trifluoromethyl)phenol (0.0565 g, 0.000287 mol) portion wise. The reaction mixture was stirred at room temperature under nitrogen for 1 hour. The reaction was diluted with ethyl acetate (15.0 mL) and washed twice with water (10.0 mL). The organic layer was separated, dried with sodium sulphate, filtered and concentrated in vacuo. The residue was dissolved in iso-propyl acetate (3.0 mL) and methanesulfonamide (0.0226 g, 0.000238 mol) and bis(tert-butylcarbonyloxy)iodobenzene (0.145 g, 0.000375 mol) were added The mixture was stirred for 5 minutes before the addition of bis[rhodium(alpha, alpha, alpha′, alpha′-tetramethyl-1,3-benzenedipropionic acid)] (0.005 g, 0.00007 mol). The reaction was stirred at 55° C. under nitrogen for 2 hours. The solvent was concentrated in vacuo to afford a crude oil, which was purified using silica gel column chromatography eluting with 0-50% EtOAc in heptanes to furnish a solid. This was further triturated in heptane:acetone (9:1 mixture, 10.0 mL) to yield the title compound as a pale orange solid (0.025 g, 19%).

Workup

  1. washwashed twice with water (10.0 mL)
  2. customThe organic layer was separated
  3. dry with materialdried with sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in iso-propyl acetate (3.0 mL)
  7. stirringThe reaction was stirred at 55° C. under nitrogen for 2 hours
  8. concentrationThe solvent was concentrated in vacuo
  9. customto afford a crude oil, which
  10. customwas purified
  11. washeluting with 0-50% EtOAc in heptanes
  12. customto furnish a solid
  13. customThis was further triturated in heptane:acetone (9:1 mixture, 10.0 mL)

Sources & evidence

ORD record
ord-30274cc6324f4b70999611283f377c82
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

Loading…