Cesium carbonate → 2-(4-Methoxy-2-methyl-phenyl)-benzo[b]thiophene-5-carboxylic acid ethyl ester

HRID 2261817Notes

Reaction equation

HRID 2261817 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=1[CH3:35].[CH2:36]([O:38][C:39]([C:41]1[CH:49]=[CH:48][C:44]2[S:45][CH:46]=[CH:47][C:43]=2[CH:42]=1)=[O:40])[CH3:37]>[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2].C(OCC)(=O)C.O.CN(C=O)C>[CH2:36]([O:38][C:39]([C:41]1[CH:49]=[CH:48][C:44]2[S:45][C:46]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=3[CH3:35])=[CH:47][C:43]=2[CH:42]=1)=[O:40])[CH3:37]

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 11776Triphenylphosphine2×HCID 1179151-Bromo-4-methoxy-2-methylbenzeneHCID 14792358HCID 14792358, compound

Product 1

HCID 574433392-(4-Methoxy-2-methyl-phenyl)-benzo[b]thiophene-5-carboxylic acid ethyl esterYield 61%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (9.70 mmol; 3.19 g) is dried in a resealable tube at 150° C. in vacuo for 2 h and cooled to room temperature. Copper(I) iodide (9.70 mmol; 1.86 g), Pd(OAc)2 (0.24 mmol; 55 mg), triphenylphosphine (0.485 mmol; 128.50 mg), 2-bromo-5-methoxytoluene (9.70 mmol; 2.14 mL), benzo[b]thiophene-5-carboxylic acid ethyl ester (4.85 mmol; 1 g) and anhydrous DMF (24 mL) are added under nitrogen atmosphere and the mixture is stirred at 140° C. After 24 h, Pd(OAc)2 (0.24 mmol; 55 mg) and triphenylphosphine (0.485 mmol; 128.50 mg) are added and the mixture is stirred for 24 more hours. The mixture is allowed to reach room temperature and water and ethyl acetate are added. The suspension is filtered through Celite® and washed with ethyl acetate. The organic layer is separated and the aqueous layer is extracted with ethyl acetate. The organic layers are combined, washed with water, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue is chromatographed (0-10% EtOAc in hexanes) to obtain the title compound (960 mg, 61%) as a colorless waxy solid. LC-ES/MS m/e 326 (M).

Workup

  1. stirringthe mixture is stirred for 24 more hours
  2. customto reach room temperature
  3. filtrationThe suspension is filtered through Celite®
  4. washwashed with ethyl acetate
  5. customThe organic layer is separated
  6. extractionthe aqueous layer is extracted with ethyl acetate
  7. washwashed with water
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is chromatographed (0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2b928a07444e486a95e6d0a1f90b9bda
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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