Water → 2-{[6-(4-Fluorophenyl)-2-naphthyl]thio}-1-methyl-1H-imidazole

HRID 735346Notes

Reaction equation

HRID 735346 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:13]=2)[CH:8]=1)(=O)=O.[CH3:26][N:27]1[CH:31]=[CH:30][N:29]=[C:28]1[SH:32].C(N(C(C)C)CC)(C)C.O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[F:23][C:20]1[CH:19]=[CH:18][C:17]([C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[C:7]([S:32][C:28]2[N:27]([CH3:26])[CH:31]=[CH:30][N:29]=2)[CH:16]=[CH:15]3)=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 866167346-(4-Fluorophenyl)-2-naphthyl trifluoromethanesulfonateHCID 178480602HCID 178480602, compound

Product 1

HCID 689751782-{[6-(4-Fluorophenyl)-2-naphthyl]thio}-1-methyl-1H-imidazoleYield 91.2%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 6-(4-fluorophenyl)-2-naphthyl trifluoromethanesulfonate (Ex 1 Step 2, 150 mg, 0.41 mmol), 1-methyl-1H-imidazole-2-thiol (47 mg, 0.41 mmol), tris(dibenzylideneacetone)dipalladium(0) (16 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (20 mg) and diisopropylethylamine (0.15 mL, 0.82 mmol) in dioxane (3 mL) was heated to 125° C. under nitrogen for 15 h. The cooled reaction mixture was poured into water and extracted with ethyl acetate (x3). The combined organic layers were washed with water and brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 25% ethyl acetate/isohexane, to give the title compound as an oil (125 mg). 1H NMR (500 MHz, CDCl3): δ 7.90 (1H, s), 7.75 (2H, t, J=8.6 Hz), 7.66-7.59 (4H, m), 7.27 (2H, m), 7.15 (2H, m), 7.10 (1H, s), 3.65 (3H, s); m/z (ES+) 335 [MH+].

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate (x3)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by flash column chromatography on silica
  7. washeluting with 25% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-534bb294fd21468294bf4222697ddd1d
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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