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

HRID 2423398Notes

Reaction equation

HRID 2423398 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:22]([O:24][CH3:25])=[O:23])=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[N:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[CH2:27][C:28]1[C:29]([C:36]2[C:41]([Cl:42])=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:43])=[N:30][O:31][C:32]=1[CH:33]([CH3:35])[CH3:34].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C>[Cl:42][C:41]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:43])[C:36]=1[C:29]1[C:28]([CH2:27][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:17]=[C:16]4[C:11]([C:12]([C:22]([O:24][CH3:25])=[O:23])=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[N:15]4)=[CH:10][CH:9]=3)=[CH:6][CH:7]=2)=[C:32]([CH:33]([CH3:35])[CH3:34])[O:31][N:30]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazoleHCID 136146135HCID 136146135, compound

Product 1

HCID 59321483Dimethyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2,4-quinolinedicarboxylateYield 46.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 75 mg (0.22 mmol) of dimethyl 7-(4-hydroxyphenyl)-2,4-quinolinedicarboxylate, 135 mg (0.44 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole and 125 mg (0.89 mmol) of K2CO3 in 2 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 62 mg (46%) of dimethyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2,4-quinolinedicarboxylate as a clear glass. 1H NMR (400 MHz, CDCl3): δ 8.88 (d, J=9.0 Hz, 1H), 8.65 (s, 1H), 8.50 (s, 1H), 7.98 (d, J=9 Hz, 1H), 7.65 (d, J=9 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 7.35-7.31 (m, 1H), 6.91 (d, J=9 Hz, 2H), 4.79 (s, 2H), 4.11 (s, 3H), 4.07 (s, 3H), 3.36 (septet, J=7 Hz, 1H), 1.44 (d, J=7 Hz, 6H). ESI-LCMS m/z 606 (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-7e644d0125824447872f94700c391078
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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