Hydrochloric Acid → HCID 21075903, compound

HRID 1373878Notes

Reaction equation

HRID 1373878 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([Cl:12])=[C:7]([OH:13])[CH:6]=[CH:5]2.[S:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH:16]=[C:15]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>[S:14]1[C:15]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8]([Cl:12])=[C:7]([OH:13])[CH:6]=[CH:5]3)=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]1=2

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 11430Potassium CarbonateHCID 220481596-Bromo-1-chloronaphthalen-2-ol

Product 1

HCID 21075903HCID 21075903, compoundYield 23.9%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
70 °C

Procedure

A mixture of 6-bromo-1-chloro-naphthalen-2-ol (11.2 g, 43.5 mmol), benzothiophene-2-boronic acid (15.1 g, 85.0 mmol) in three portions, palladium (II) acetate (0.76 g, 3.43 mmol) in three portions, potassium carbonate (30.1 g, 224 mmol) in three portions, tetrabutylammonium bromide (14.0 g, 43.5 mmol) in water (65 mL) and THF (40 mL) was heated at 70° C. for 8.5 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 and solvent evaporated. The residue was purified by flash chromatography using 100% chloroform, 30–50% 1,2-dichloroethane in hexane and 20–30% 1,2-dichloroethane in hexane (Biotage apparatus) eluent. Drying at 60° C. in vacuo for 20 minutes yielded 6-benzo[b]thiophen-2-yl-1-chloro-naphthalen-2-ol as a beige-yellow solid (3.22 g, 23.9%) MP: 220–1° C.; Mass spectrum (−ES, [M−H]−) m/z 309/311. 1H NMR (500 MHz, DMSO-d6): δ 10.64 (s, 1H), 8.26 (d, 1H, J=1.73 Hz), 8.11 (d, 1H, J=8.85 Hz), 8.05 (dd, 1H, J=8.85 and 1.83 Hz), 7.95–8.01 (m, 2H), 7.87–7.92 (m, 2H), 7.33–7.43 ppm (m, 3H). Elemental Analysis for C18H11ClOS: Calcd: C, 69.56; H, 3.57; N, 0.00; Found: C, 69.58; 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
  6. customsolvent evaporated
  7. customThe residue was purified by flash chromatography
  8. customDrying at 60° C. in vacuo for 20 minutes

Sources & evidence

ORD record
ord-9b0ac81a2f324e9cbaaea8c626923e6a
Source dataset
uspto-grants-2007_01
Patent number
US07163954B2

Reaction notes

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