Ethyl Acetate → HCID 117653246, compound

HRID 2178108Notes

Reaction equation

HRID 2178108 reaction equation
Br[C:2]1[C:3]([O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[C:34]([F:40])[CH:33]=2)=[CH:4][C:5]([F:30])=[C:6]([S:8]([N:11](CC2C=CC(OC)=CC=2OC)[C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][N:13]=2)(=[O:10])=[O:9])[CH:7]=1.CCOC(C)=O>C1COCC1.CC(O)=O.O.[Zn]>[C:38]([C:35]1[CH:36]=[CH:37][C:32]([O:31][C:3]2[CH:2]=[CH:7][C:6]([S:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][N:13]=3)(=[O:10])=[O:9])=[C:5]([F:30])[CH:4]=2)=[CH:33][C:34]=1[F:40])#[N:39]

Participants

7

Reactant 2

HCID 8857Ethyl AcetateHCID 117653514HCID 117653514, compound

Product 1

HCID 117653246HCID 117653246, compoundYield 26%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-4-(4-cyano-3-fluorophenoxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide (Preparation 1, 220 mg, 0.35 mmol) in THF (8 mL), AcOH (10 mL) and water (2.5 mL) was added zinc dust (800 mg, 12.2 mmol). The reaction mixture was left to stir at room temperature for 70 hours. To the reaction mixture was added EtOAc (25 mL) and the mixture filtered through celite and washed with EtOAc (50 mL). The filtrate was retained and to this was added saturated aqueous NaHCO3 (80 mL). The organic layer was retained, dried over MgSO4, and the solvent removed in vacuo. The residue was purified using reverse phase column chromatography eluting with acetonitrile and water (acidic). The residue was dissolved in DCM and treated with TFA (0.3 mL) and stirred at room temperature for 1 hour. The reaction was concentrated in vacuo azeotroping with MeOH. The residue was purified using preparative HPLC to afford the title compound as a colourless powder (16 mg, 26%).

Workup

  1. waitThe reaction mixture was left
  2. filtrationthe mixture filtered through celite
  3. washwashed with EtOAc (50 mL)
  4. additionto this was added saturated aqueous NaHCO3 (80 mL)
  5. dry with materialdried over MgSO4
  6. customthe solvent removed in vacuo
  7. customThe residue was purified
  8. washeluting with acetonitrile and water (acidic)
  9. dissolutionThe residue was dissolved in DCM
  10. additiontreated with TFA (0.3 mL)
  11. stirringstirred at room temperature for 1 hour
  12. concentrationThe reaction was concentrated in vacuo
  13. customazeotroping with MeOH
  14. customThe residue was purified

Sources & evidence

ORD record
ord-12f8b5c55c3e4e299b63fab34280df2c
Source dataset
uspto-grants-2015_06
Patent number
US09067922B2

Reaction notes

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