Potassium Carbonate → 6-(benzylthio)-1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-one

HRID 1504491Notes

Reaction equation

HRID 1504491 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[CH:24]=[C:23]([Cl:25])[C:22](Br)=[CH:21][C:20]=1[O:27][CH3:28])[C:14](=[O:29])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[C:20]([O:27][CH3:28])=[CH:21][C:22]([C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([F:30])[CH:36]=3)=[C:23]([Cl:25])[CH:24]=1)[C:14](=[O:29])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 1177373026-(benzylthio)-1-(4-bromo-5-chloro-2-methoxyphenyl)quinolin-2(1H)-one

Product 1

HCID 1177370126-(benzylthio)-1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-oneYield 81%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A screw cap vial was charged with 6-(benzylthio)-1-(4-bromo-5-chloro-2-methoxyphenyl)quinolin-2(1H)-one (1.22 g, 2.506 mmol), (3-fluorophenyl)boronic acid (0.526 g, 3.76 mmol), potassium carbonate (1.039 g, 7.52 mmol) and Pd(Ph3P)4 (0.290 g, 0.251 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (9.4 ml) and water (3.1 ml) were added in sequence. The reaction was heated to 90° C. for 1 hour. The mixture was diluted with NH4Cl and extracted with EtOAc (3×). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 0-50% EtOAc/Heptane) to give 6-(benzylthio)-1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinolin-2(1H)-one (1.02 g, 2.03 mmol, 81% yield) as a cream-colored solid. m/z (ESI) 502.2 (M+H)+.

Workup

  1. customA screw cap vial
  2. customThe vial was flushed with Ar (g)
  3. addition1,4-dioxane (9.4 ml) and water (3.1 ml) were added in sequence
  4. additionThe mixture was diluted with NH4Cl
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 0-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-f7c84e1d7c74409bb8c79a99c9d1f03f
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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