Iodoethane → 7-(Ethyloxy)-3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245175Notes

Reaction equation

HRID 245175 reaction equation
I[CH2:2][CH3:3].[OH:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([C:26]([O:28]C)=[O:27])=[C:10]([CH3:25])[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)=[N:12]2)=[CH:7][C:6]=1[S:30]([CH3:33])(=[O:32])=[O:31].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O>[CH2:2]([O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([C:26]([OH:28])=[O:27])=[C:10]([CH3:25])[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=3)=[N:12]2)=[CH:7][C:6]=1[S:30]([CH3:33])(=[O:32])=[O:31])[CH3:3]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 10796Cesium carbonateHCID 136338340Methyl 7-hydroxy-3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 674175377-(Ethyloxy)-3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Iodoethane (1.10 mL, 13.65 mL) was slowly added to a mixture of methyl 7-hydroxy-3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (3.0 g, 6.83 mmol) and Cs2CO3 (6.67 g, 20.48 mmol) in N,N-dimethylformamide (30 mL) at room temperature. The reaction mixture was stirred overnight, quenched with saturated NH4Cl, and extracted with methylene chloride (three times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 120 g silica, 0-20% ethyl acetate/methylene chloride) to afford 7-(ethyloxy)-3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (2.92 g, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ8.25 (s, 1H), 7.98-8.06 (m, 2H), 7.92 (d, J=8.03 Hz, 1H), 7.76-7.83 (m, 2H), 4.40 (q, J=6.94 Hz, 2H), 4.09 (s, 3H), 2.37 (s, 3H), 1.47 (t, J=6.90 Hz, 3H); MS (m/z) 468.1 (M+H+).

Workup

  1. customquenched with saturated NH4Cl
  2. extractionextracted with methylene chloride (three times)
  3. washThe combined organic extracts were washed with brine (two times)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via column chromatography (ISCO, 120 g silica, 0-20% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-5bf9ea3e742445b598fb4f799fe1cd13
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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