Hydrochloric Acid → HCID 21075902, compound

HRID 1373861Notes

Reaction equation

HRID 1373861 reaction equation
[Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8](Br)=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:13][CH2:14][C:15]#[N:16].[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[CH:19]=[C:18]1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[S:17]1[C:18]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[C:2]([Br:1])=[C:3]([O:13][CH2:14][C:15]#[N:16])[CH:4]=[CH:5]3)=[CH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]1=2

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 11430Potassium CarbonateHCID 11493856HCID 11493856, compound

Product 1

HCID 21075902HCID 21075902, compoundYield 63.9%

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)-acetonitrile (9.2 g, 27 mmol), benzothiophene-2-boronic acid (7.2 g, 40 mmol) in two portions, tetrabutylammonium bromide (8.7 g, 27 mmol), potassium carbonate (9.4 g 68 mmol) and palladium (II) acetate (0.079 g, 0.35 mmol) in THF (25 mL) and water (41 mL) was heated at 70° C. for seven hours. After cooling to ambient temperature, the reaction mixture was poured into 2N hydrochloric acid. This was extracted with hot chloroform (due to limited solubility). The organic phase was washed with water and brine. It was then dried with anhydrous magnesium sulfate, filtrered and solvent evaporated. The residue was stirred in acetonitrile for ten minutes. It was then filtered and rinsed with acetonitrile. The precipitate was dried for 12 hours in vacuo at 76° C. to yield 6.8 g of title compound as a taupe-colored solid. The filtrate was concentrated and purified by flash chromatography with 10–45% chloroform in hexane. After drying for 20 minutes in vacuo at 60° C., 1.33 g more of the title compound was obtained as a light buff-colored solid. The total yield of (6-benzo[b]thiophen-2-yl-1-bromo-naphthalen-2-yloxy)-acetonitrile was 8.1 g (86%): MP: 179–81° C.; Mass spectrum (+EI, M+) m/z 393/395. 1H NMR (500 MHz, DMSO-d6): δ8.37 (d, 1H,J=1.83 Hz), 8.20 (d, 2H, J=7.94 Hz), 8.15 (dd, 1H, J=8.86 and 1.87 Hz), 8.01–4 (m, 2H), 7.88–7.90 (m, 1H), 7.67 (d, 1H, J=9.16 Hz), 7.37–7.43 (m, 2H), 5.44 ppm (s, 2H). Elemental Analysis for C20H12BrNOS: Calcd: C, 60.92; H, 3.07; N, 3.55; Found: C, 60.75; H, 2.91; N, 3.34.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionThis was extracted with hot chloroform (due to limited solubility)
  3. washThe organic phase was washed with water and brine
  4. dry with materialIt was then dried with anhydrous magnesium sulfate
  5. customsolvent evaporated
  6. filtrationIt was then filtered
  7. washrinsed with acetonitrile
  8. customThe precipitate was dried for 12 hours in vacuo at 76° C.

Sources & evidence

ORD record
ord-8639ae6c213e4084b6ee1ae4814276db
Source dataset
uspto-grants-2007_01
Patent number
US07163954B2

Reaction notes

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