Ethylene Glycol → 2-{[6-(2,4-Difluorophenyl)-2-naphthyl]thio}benzonitrile

HRID 735307Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([SH:19])[CH:13]=[CH:12]2.I[C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]#[N:24].C(=O)([O-])[O-].[K+].[K+].C(O)CO>C(O)(C)C.[Cu]I.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([S:19][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]#[N:24])[CH:13]=[CH:12]2

Participants

Conditions

Temperature: 80 °C

Procedure

6-(2,4-Difluorophenyl)-2-naphthyl hydrosulfide (Step 2, 0.78 g) was dissolved in isopropyl alcohol (15 mL). 2-Iodobenzonitrile (0.66 g, 2.88 mmol), copper(I) iodide (29 mg, 0.15 mmol), potassium carbonate (0.8 g, 5.79 mmol) and ethylene glycol (320 μL) were added and the reaction heated to 80° C. under nitrogen overnight. Ethyl acetate was added to the cooled reaction mixture and stirred for 15 minutes. The mixture was filtered and the filtrate evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 10-20% ethyl acetate/isohexane, followed by recrystallisation from ethyl acetate/isohexane, to give 2-{[6-(2,4-difluorophenyl)-2-naphthyl]thio}benzonitrile (216 mg, 20%). 1H NMR (500 MHz, CDCl3) δ 8.04 (1H, s), 7.97 (1H, s), 7.88 (2H, t, J=7.8 Hz), 7.68 (2H, d, J=8.0 Hz), 7.54-7.48 (2H, m), 7.43-7.39 (1H, m), 7.28 (1H, t, J=7.6 Hz), 7.19 (1H, d, J=7.9 Hz), 7.03-6.95 (2H, m).

Workup

filtrationThe mixture was filtered
customthe filtrate evaporated in vacuo
customThe residue was purified by flash column chromatography on silica
washeluting with 10-20% ethyl acetate/isohexane
customfollowed by recrystallisation from ethyl acetate/isohexane

Sources & evidence

ORD record: ord-f6438c4c933b4f62ab5370b0a7332d8c
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592456B2

Reaction notes

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