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

HRID 2423402Notes

Reaction equation

HRID 2423402 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([C:12]([C:18]([O:20][CH3:21])=[O:19])=[CH:13][CH:14]=[N:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[CH2:23][C:24]1[C:25]([C:32]2[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:39])=[N:26][O:27][C:28]=1[CH:29]([CH3:31])[CH3:30].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C>[Cl:38][C:37]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:39])[C:32]=1[C:25]1[C:24]([CH2:23][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:17]=[C:16]4[C:11]([C:12]([C:18]([O:20][CH3:21])=[O:19])=[CH:13][CH:14]=[N:15]4)=[CH:10][CH:9]=3)=[CH:6][CH:7]=2)=[C:28]([CH:29]([CH3:31])[CH3:30])[O:27][N:26]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazoleHCID 136146134Methyl 7-(4-hydroxyphenyl)-4-quinolinecarboxylate

Product 1

HCID 59321577Methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-4-quinolinecarboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 90 mg (0.32 mmol) of methyl 7-(4-hydroxyphenyl)-4-quinolinecarboxylate, 196 mg (0.64 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole and 178 mg (1.29 mmol) of K2CO3 in 2.5 mL DMF was stirred at ambient temperature for 60 hr. EtOAc was added and the mixture washed with three portions of H2O then brine. The solution was concentrated and the residue purified by silica gel chromatography (12 g of silica gel eluting with 0-50% EtOAc in hexanes over 45 minutes) to give 98 mg (56%) of methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-4-quinolinecarboxylate as a clear glass. 1H NMR (400 MHz, CDCl3): δ 9.02 (d, J=4 Hz, 1H), 8.81 (d, J=9 Hz, 1H), 8.29 (s, 1H), 7.88-7.85 (m, 2H), 7.64 (d, J=8 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 7.35-7.32 (m, 1H), 6.91 (d, J=8 Hz, 2H), 4.79 (s, 2H), 4.05 (s, 3H), 3.34 (septet, J=7 Hz, 1H), 1.43 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.

Workup

  1. washthe mixture washed with three portions of H2O
  2. concentrationThe solution was concentrated
  3. customthe residue purified by silica gel chromatography (12 g of silica gel eluting with 0-50% EtOAc in hexanes over 45 minutes)

Sources & evidence

ORD record
ord-e817e9d014ad498ea81f46d9515471f5
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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