Ethyl Acetate → 6-Methoxy-3-(4-methoxy-benzylsulfanyl)-quinoline-4-carboxylic acid methyl ester

HRID 2273186Notes

Reaction equation

HRID 2273186 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][C:6]=1OS(C(F)(F)F)(=O)=O)=[O:4].[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][SH:34])=[CH:29][CH:28]=1.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>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>[CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][C:6]=1[S:34][CH2:33][C:30]1[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=1)=[O:4]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 804074-Methoxy-alpha-toluenethiolHCID 81531DiisopropylethylamineHCID 866715286-Methoxy-3-trifluoromethanesulfonyloxy-quinoline-4-carboxylic acid methyl ester

Product 1

HCID 672486216-Methoxy-3-(4-methoxy-benzylsulfanyl)-quinoline-4-carboxylic acid methyl esterYield 88.4%

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

Procedure

A mixture of 6-methoxy-3-trifluoromethanesulfonyloxy-quinoline-4-carboxylic acid methyl ester (3.69 g, 10.10 mmol, 1.0 eq), (4-methoxy-phenyl)-methanethiol (3.43 g, 22.22 mmol, 2.2 eq), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (409 mg, 0.71 mmol, 0.07 eq), tris(dibenzylideneacetone)dipalladium(0) (925 mg, 1.01 mmol, 0.1 eq) and N,N-diisopropylethylamine (3.46 mL, 20.20 mmol, 2.0 eq) in dioxane (40 mL) is heated under reflux for 16 hours, then filtered through decalite and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 5:1, v/v) to afford 6-methoxy-3-(4-methoxy-benzylsulfanyl)-quinoline-4-carboxylic acid methyl ester as an off-white solid (3.30 g, 88% yield).

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 16 hours
  3. filtrationfiltered through decalite
  4. concentrationconcentrated
  5. customto give a residue that
  6. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-9e5f2913e41841a9a3fc051adc77cf4a
Source dataset
uspto-grants-2015_09
Patent number
US09120822B2

Reaction notes

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