Hydrochloric Acid → HCID 69410849, compound

HRID 1373865Notes

Reaction equation

HRID 1373865 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12](Br)[CH:13]=2)[C:8]=1[Br:18])[CH3:2].[S:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH:22]=[C:21]1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4](=[O:19])[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:21]3[S:20][C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[CH:22]=3)[CH:13]=2)[C:8]=1[Br:18])[CH3:2]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 11430Potassium CarbonateHCID 981253(1,6-Dibromo-naphthalen-2-yloxy)-acetic acid ethyl ester

Product 1

HCID 69410849HCID 69410849, compoundYield 42%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (1,6-dibromo-naphthalen-2-yloxy)-acetic acid ethyl ester (6.9 g, 18 mmol), benzothiophene-2-boronic acid (4.78 g, 26.8 mmol) in two portions, palladium (II) acetate (0.11 g, 0.49 mmol), potassium carbonate (6.2 g, 45 mmol), tetrabutylammonium bromide (5.8 g, 18 mmol) in water (90 mL) and THF (35 mL) was heated at 70° C. for 3.5 hours. The reaction mixture was allowed to cool to ambient temperature and then poured into excess 2N hydrochloric acid. It was extracted with chloroform. The organic phase was then washed with water and brine. It was dried with anhydrous magnesium sulfate, filtered hot (due to limited solubility) and solvent evaporated. The residue was purified by flash chromatography using 25–45% methylene chloride in hexane and 100% chloroform as eluent. Drying at 60° C. in vacuo for 30 minutes yielded (6-benzo[b]thiophen-2-yl-1-bromo-naphthalen-2-yloxy)-acetic acid ethyl ester as a buff-colored solid (3.3 g, 42%) MP: 178–81° C.; mass spectrum (+EI, M+) m/z 440/442. 1H NMR (500 MHz, DMSO-d6): δ8.32 (d, 1H,J=1.83 Hz), 8.18 (d, 1H, J=8.86 Hz), 8.07–8.12 (m, 2H), 8.01 (d, 2H, J=7.33 Hz), 7.88 (dd, 1H, J=7.63 Hz and 1.07 Hz), 7.47 (d, 1H, J=9.16 Hz), 7.36–7.43 (m, 2H), 5.09 (s, 2H), 4.18 (q, 2H, J=7.08 Hz), 1.22 ppm (t, 3H, J=7.11 Hz). Elemental Analysis for C22H17BrO3S: Calcd: C, 59.87; H, 3.88; N, 0.00; Found: C, 60.03; H, 3.83; N, 0.00.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionIt was extracted with chloroform
  3. washThe organic phase was then washed with water and brine
  4. dry with materialIt was dried with anhydrous magnesium sulfate
  5. filtrationfiltered hot (due to limited solubility) and solvent
  6. customevaporated
  7. customThe residue was purified by flash chromatography
  8. customDrying at 60° C. in vacuo for 30 minutes

Sources & evidence

ORD record
ord-305b44b5097e4c1890d3e8734962a93a
Source dataset
uspto-grants-2007_01
Patent number
US07163954B2

Reaction notes

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