Benzoic acid, 2-mercapto-, methyl ester → Methyl 2-{[2-(4-fluorophenyl)quinolin-6-yl]thio}benzoate

HRID 735332Notes

Reaction equation

HRID 735332 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[CH:6]=[CH:5]2.[C:19]([O:28][CH3:29])(=[O:27])[C:20]1[C:21](=[CH:23][CH:24]=[CH:25][CH:26]=1)[SH:22].C(N(CC)C(C)C)(C)C.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>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]>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:7]2[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([S:22][C:21]4[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=4[C:19]([O:28][CH3:29])=[O:27])[CH:3]=3)[N:8]=2)=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 21009Benzoic acid, 2-mercapto-, methyl esterHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 689034326-Bromo-2-(4-fluorophenyl)quinoline

Product 1

HCID 68901056Methyl 2-{[2-(4-fluorophenyl)quinolin-6-yl]thio}benzoateYield 90%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-bromo-2-(4-fluorophenyl)quinoline (Example 19 Step 1; 758 mg, 2.51 mmol), methyl thiosalicylate (0.35 mL, 2.54 mmol), N,N-diisopropylethylamine (0.87 mL, 4.99 mmol), tris(dibenzylideneacetone)dipalladium(0) (58 mg, 0.063 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (74 mg, 0.128 mmol) in 1,4-dioxane (15 mL) was degassed then heated at reflux under nitrogen for 15 hours. The reaction mixture was allowed to cool, concentrated in vacuo and the residue purified by flash chromatography, eluting with 15-25% ethyl acetate/isohexane, to afford methyl 2-{[2-(4-fluorophenyl)quinolin-6-yl]thio}benzoate (0.876, 90%). 1H NMR (400 MHz, CDCl3) δ 8.20-8.14 (4H, m), 8.08 (1H, d, J 1.9 Hz), 8.01 (1H, dd, J 1.6, 7.8 Hz), 7.88 (1H, d, J 8.6 Hz), 7.76 (1H, dd, J 2.0, 8.7 Hz), 7.23-7.15 (4H, m), 6.91 (1H, dd, J 0.9, 8.0 Hz), 3.97 (3H, s); m/z (ES+) 390 [MH+].

Workup

  1. customwas degassed
  2. temperaturethen heated
  3. temperatureat reflux under nitrogen for 15 hours
  4. temperatureto cool
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by flash chromatography
  7. washeluting with 15-25% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-4fea7591db8547ea8af3717ab2e8db08
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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