1,4-Dioxane → 4-(3-Chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluoro-N-(methylsulfonyl)benzamide

HRID 508408Notes

Reaction equation

HRID 508408 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[C:13]([Cl:21])[CH:12]=2)=[CH:4][C:3]=1[F:22].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[CH3:41][S:42]([NH2:45])(=[O:44])=[O:43].S([O-])(O)(=O)=O.[K+].[O:52]1CCOC[CH2:53]1>C(Cl)Cl.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[Cl:21][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[C:17]([F:20])([F:19])[F:18])[CH2:10][O:9][C:5]1[C:6]([F:8])=[CH:7][C:2]([C:53]([NH:45][S:42]([CH3:41])(=[O:44])=[O:43])=[O:52])=[C:3]([F:22])[CH:4]=1

Participants

8

Reactant 5

HCID 312751,4-DioxaneHCID 72879MethanesulfonamideHCID 516920Potassium bisulfateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 866825541-Bromo-4-(3-chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluorobenzene

Product 1

HCID 866825534-(3-Chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluoro-N-(methylsulfonyl)benzamideYield 26%

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 1-bromo-4-(3-chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluorobenzene (Preparation 19, 200 mg, 0.50 mmol) in 1,4-dioxane (2.0 mL) were added molybdenumhexacarbonyl (142 mg, 0.50 mmol), trans-bis(acetate)bis[(o-(di-o-tolylphosphino)benzyl]dipalladium (II) (23 mg, 0.025 mmol), tri-tertbutylphosphonium tetrafluoroborate (14 mg, 0.050 mmol), 1,8-diazobicylco[5.4.0]undec-7-ene (223 μL, 1.49 mmol) and methanesulphonamide (142 mg, 1.49 mmol). The reaction mixture was heated in the microwave at 140° C. for 20 minutes. The solvent was then evaporated in vacuo to yield a brown oil, which was dissolved in DCM (20 mL). Potassium hydrogen sulphate (30 mL) was added and the organic layer separated. The aqueous layer was extracted with DCM (2×20 mL), then the combined organics were washed with brine (50 mL), filtered through a phase separator and reduced to dryness to give a brown solid, which was purified by silica gel chromatography eluting with 2 to 10% methanol in DCM to yield the title compound as white solid (57 mg, 26%).

Workup

  1. customThe solvent was then evaporated in vacuo
  2. customto yield a brown oil, which
  3. customthe organic layer separated
  4. extractionThe aqueous layer was extracted with DCM (2×20 mL)
  5. washthe combined organics were washed with brine (50 mL)
  6. filtrationfiltered through a phase separator
  7. customto give a brown solid, which
  8. customwas purified by silica gel chromatography
  9. washeluting with 2 to 10% methanol in DCM

Sources & evidence

ORD record
ord-cb88853f0c344800a40c0039fbd6f755
Source dataset
uspto-grants-2015_08
Patent number
US09096500B2

Reaction notes

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