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

HRID 2423388Notes

Reaction equation

HRID 2423388 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[CH:12]=[CH:11]3)=[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-].[Cs+].[Cs+].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:7]=[CH:6][C:5]([C:8]3[CH:9]=[C:10]4[C:15](=[CH:16][CH:17]=3)[N:14]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[CH:12]=[CH:11]4)=[CH:4][CH:3]=2)=[C:28]([CH:29]([CH3:31])[CH3:30])[O:27][N:26]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazole2×HCID 59321540Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate

Product 1

HCID 59321513Methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (222 g, 0.8 mol), 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole (292 g, 0.96 mol) and cesium carbonate (312 g, 0.96 mol) in DMF (1.5 L) was heated at 65° C. for 28 hours. Additional 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole (105 g, 0.34 mol) dissolved in DMF (150 mL) was added. The mixture was cooled to room temperature and poured into water (5 L) with stirring. The resulting taffy was separated from the supernatant and stirred with ethyl acetate (2.5 L) for 3 hours at room temperature. The resulting suspension was filtered and the filter cake was dried to yield methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate as a solid (245 g, 56%). 1H NMR (400 MHz, DMSO-d6): δ 8.54 (d, J=9 Hz, 1H), 8.28 (d, J=1 Hz, 1H), 8.11 (m, 3H), 7.72 (d, J=9 Hz, 2H), 7.62 (d, J=8 Hz, 2H), 7.53 (m, 1H), 6.93 (d, J=9 Hz, 2H), 4.88 (s, 2H), 3.93 (s, 3H), 3.47 (m, 1H), 1.33 (d, J=7 Hz, 6H). ES-LCMS m/z 547 (M+H)+.

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to room temperature
  3. customThe resulting taffy was separated from the supernatant
  4. stirringstirred with ethyl acetate (2.5 L) for 3 hours at room temperature
  5. filtrationThe resulting suspension was filtered
  6. customthe filter cake was dried

Sources & evidence

ORD record
ord-117fb6c530824cdfad8686a9107e27a1
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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