Hydrochloric Acid → 2-(4-Hydroxy-2-methyl-phenyl)-benzo[b]thiophene-7-carboxylic acid ethyl ester

HRID 2261820Notes

Reaction equation

HRID 2261820 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11]2[S:12][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:5])[CH3:2].Br[C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][C:26]=1[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11]2[S:12][C:13]([C:25]3[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][C:26]=3[CH3:32])=[CH:14][C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:5])[CH3:2]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 728574-Bromo-m-cresolHCID 67527887Ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophene-7-carboxylate

Product 1

HCID 687769702-(4-Hydroxy-2-methyl-phenyl)-benzo[b]thiophene-7-carboxylic acid ethyl esterYield 44%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophene-7-carboxylic acid ethyl ester (1.04 mmoles; 345.00 mg) in anhydrous DMF (2.5 mL) is added, under nitrogen atmosphere, via syringe pump (3 mL/2 h) to a suspension at 80° C. of 4-bromo-3-methylphenol (1.04 mmoles; 194.23 mg), Cesium carbonate (2.08 mmoles; 683.53 mg), Pd(OAc)2 (103.84 μmoles; 23.55 mg), 1,1′-bis(diphenylphosphino)ferrocene (311 μmoles; 176 mg) in anhydrous DMF (1.6 mL). The mixture is stirred at 80° C. for 1 h and allowed to reach room temperature. The reaction is poured into a mixture of ethyl acetate and HCl (1M), filtered through Celite® and washed with ethyl acetate. The organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×20 mL). The organic layers are combined, washed with water, dried (Na2SO4), filtered and concentrated. The residue is chromatographed (10-40% EtOAc in hexanes) to obtain the title compound (143 mg, 44%) as a white solid. LC-ES/MS m/e 311 (M−1).

Workup

  1. customto reach room temperature
  2. filtrationfiltered through Celite®
  3. washwashed with ethyl acetate
  4. customThe organic layer is separated
  5. extractionthe aqueous layer is extracted with ethyl acetate (2×20 mL)
  6. washwashed with water
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue is chromatographed (10-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b1f4a517ea5442bf9244f1b725d3fe57
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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