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Potassium Carbonate → Methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate

HRID 2423395
Notes
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Reaction equation

HRID 2423395 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)O1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl[CH2:60][C:61]1[C:62]([C:69]2[C:74]([Cl:75])=[CH:73][CH:72]=[CH:71][C:70]=2[Cl:76])=[N:63][O:64][C:65]=1[CH:66]([CH3:68])[CH3:67].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.CN(C=O)C.O>[Cl:75][C:74]1[CH:73]=[CH:72][CH:71]=[C:70]([Cl:76])[C:69]=1[C:62]1[C:61]([CH2:60][O:30][C:27]2[CH:26]=[CH:25][C:24]([C:2]3[CH:11]=[C:10]4[C:5]([CH:6]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[N:9]4)=[CH:4][CH:3]=3)=[CH:29][CH:28]=2)=[C:65]([CH:66]([CH3:68])[CH3:67])[O:64][N:63]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

12

Reactant 6

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazoleHCID 59321547Methyl 7-bromoquinoline-3-carboxylate

Product 1

HCID 59321510Methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylateYield 40.9%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 78 mg (0.29 mmol) of methyl 7-bromo-3-quinolinecarboxylate, 97 mg (0.44 mmol) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, 3 mg (0.01 mmol) of palladium acetate, 8 mg (0.03 mmol) of triphenylphosphine, 218 mg (1.03 mmol) of K3PO4 and 25 μL of H2O in 1.0 mL of dioxane was stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with water and brine then concentrated. To the residue was added 65 mg (0.21 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole, 74 mg (0.54 mmol) of K2CO3 and 1.5 mL of DMF and the mixture was then stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with three portions of water, then brine. The solution was concentrated and the residue purified by silica gel chromatography (12 g of silica gel eluting with 0-40% EtOAc in hexanes over 45 minutes) to give 47 mg (30%) of methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate as a clear glass. 1H NMR (400 MHz, CDCl3): δ 9.44 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 7.96 (d, J=9 Hz, 1H), 7.82 (d, J=9 Hz, 1H), 7.64 (d, J=9 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 7.35-7.31 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.79 (s, 2H), 4.02 (s, 3H), 3.38-3.34 (m, 1H), 1.45 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.

Workup

  1. washthe organics were washed with water and brine
  2. concentrationthen concentrated
  3. washthe organics were washed with three portions of water
  4. concentrationThe solution was concentrated
  5. customthe residue purified by silica gel chromatography (12 g of silica gel eluting with 0-40% EtOAc in hexanes over 45 minutes)

Sources & evidence

ORD record
ord-27ec22573b4c4f218385e03196a04c0a
Source dataset
uspto-grants-2011_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07960552B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes