Methanol → 6-(benzylthio)-1-(4-bromo-2-methoxyphenyl)quinolin-2(1H)-one

HRID 1504473Notes

Reaction equation

HRID 1504473 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[CH:11][C:12]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][C:24]=2[O:30][CH3:31])=[C:13](/[CH:15]=[CH:16]/[C:17]([O:19]CC)=O)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C[O-].[Na+]>C(Cl)Cl>[CH2:1]([S:8][C:9]1[CH:14]=[C:13]2[C:12](=[CH:11][CH:10]=1)[N:22]([C:23]1[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][C:24]=1[O:30][CH3:31])[C:17](=[O:19])[CH:16]=[CH:15]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 117746872(E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylate

Product 1

HCID 1177371856-(benzylthio)-1-(4-bromo-2-methoxyphenyl)quinolin-2(1H)-oneYield 68.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A RBF was charged with (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylate (3.13 g, 6.28 mmol) and MeOH (31.4 ml) to give a yellow suspension. Sodium methoxide (25 wt % in MeOH) (0.271 ml, 1.256 mmol) was added. A reflux condenser was attached, and the flask was lowered into a 75° C. heating bath. The bath quickly spiked to ca. 80-85° C., but returned to 70-75° C. after 30 min. The reaction was stirred for 16 hrs, and the mixture was diluted with DCM and concentrated. The residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 25-g silica gel loading column, 10-60% EtOAc/Heptane) to give 6-(benzylthio)-1-(4-bromo-2-methoxyphenyl)quinolin-2(1 H)-one (1.95 g, 4.31 mmol, 68.6% yield) as a yellow solid. 1 H NMR (400 MHz, DMSO-d6) □=7.94 (d, J=9.5 Hz, 1 H), 7.78 (d, J=2.2 Hz, 1 H), 7.50 (d, J=2.1 Hz, 1 H), 7.43-7.16 (m, 8 H), 6.66 (d, J=9.6 Hz, 1 H), 6.47 (d, J=8.8 Hz, 1 H), 4.23 (s, 2 H), 3.69 (s, 3 H). m/z (ESI) 452.0 (M+H)+.

Workup

  1. customto give a yellow suspension
  2. customA reflux condenser was attached
  3. customwas lowered into a 75° C.
  4. temperatureheating bath
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 25-g silica gel loading column, 10-60% EtOAc/Heptane)

Sources & evidence

ORD record
ord-aadff96454364b39855bf88d76d5522a
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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