Cesium fluoride → Tert-butyl(4-(2,4-dimethyl-1,3-thiazol-5-yl)-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate

HRID 2390248Notes

Reaction equation

HRID 2390248 reaction equation
[C:1]([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[C:16]#[C:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH2:27][CH2:28][CH3:29])(=[O:26])=[O:25])[CH:19]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:31][C:32]1[S:33][C:34](B2OC(C)(C)C(C)(C)O2)=[C:35]([CH3:37])[N:36]=1.[F-].[Cs+]>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:34]2[S:33][C:32]([CH3:31])=[N:36][C:35]=2[CH3:37])=[CH:11][C:10]=1[C:16]#[C:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH2:27][CH2:28][CH3:29])(=[O:26])=[O:25])[CH:19]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 185257002,4-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazoleHCID 56593972Tert-butyl(4-bromo-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate2×

Product 1

HCID 58521912Tert-butyl(4-(2,4-dimethyl-1,3-thiazol-5-yl)-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl(4-bromo-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate (Intermediate 191; 100 mg; 0.20 mmol), 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole (73 mg; 0.30 mmol) was placed in a microwave vial and treated with caesium fluoride (93 mg; 0.61 mmol) and bis(triphenylphosphine)palladium(II) chloride (14 mg; 0.02 mmol). The tube was sealed and degased with N2 before adding dioxane (2 ml) and water (1 ml). The resulting reaction mixture was irradiated in a microwave reactor at 120° C. for 10 minutes. The reaction mixture was taken up in EtOAc and washed with water and brine. The organic phase was dried over MgSO4, filtered, concentrated and purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc affording the title compound as a brown sticky solid (78 mg, 73%).

Workup

  1. customThe tube was sealed
  2. customdegased with N2
  3. additionbefore adding dioxane (2 ml) and water (1 ml)
  4. customThe resulting reaction mixture
  5. customwas irradiated in a microwave reactor at 120° C. for 10 minutes
  6. washwashed with water and brine
  7. dry with materialThe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash column chromatography (silica)
  11. washeluting with cyclohexane containing
  12. temperatureincreasing amounts of EtOAc affording the title compound as a brown sticky solid (78 mg, 73%)

Sources & evidence

ORD record
ord-b77ffa87d825469aa34d047b41612afa
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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