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

HRID 2423511Notes

Reaction equation

HRID 2423511 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[N:20]=[C:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:18]=[CH:17]3)=[CH:10][C:9]=1[CH3:29].Cl[CH2:31][C:32]1[C:33]([C:40]2[C:45]([Cl:46])=[CH:44][CH:43]=[CH:42][C:41]=2[Cl:47])=[N:34][O:35][C:36]=1[CH:37]([CH3:39])[CH3:38].O>CN(C)C=O>[Cl:46][C:45]1[CH:44]=[CH:43][CH:42]=[C:41]([Cl:47])[C:40]=1[C:33]1[C:32]([CH2:31][O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[C:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:18]=[CH:17]4)=[CH:10][C:9]=2[CH3:29])=[C:36]([CH:37]([CH3:39])[CH3:38])[O:35][N:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazoleHCID 59321464HCID 59321464, compound

Product 1

HCID 59321528Ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)-3-methylphenyl]-2-quinolinecarboxylateYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cesium carbonate (54.9 mg, 168.6 μmol) was added to ethyl 6-(4-hydroxy-3-methylphenyl)-2-quinolinecarboxylate (47.1 mg, 153.3 μmol) and 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole (51.3 mg, 168.6 μmol) in N,N-dimethylformamide (3.1 mL) at room temperature. The resulting suspension was stirred for twenty hours, then water was added and the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 3:7 ethyl acetate:hexanes to give 19.1 mg (22%) of ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)-3-methylphenyl]-2-quinolinecarboxylate as an oil. 1H NMR (400 MHz, d6-DMSO): δ 8.56 (d, J=9 Hz, 1H), 8.28 (s, 1H), 8.19-8.09 (m, 3H), 7.66-7.59 (m, 4H), 7.55 (dd, J=9, 7 Hz, 1H), 7.09 (d, J=9 Hz, 1H), 4.91 (s, 2H), 4.42 (q, J=7 Hz, 2H), 3.52 (septet, J=7 Hz, 1H), 1.97 (s, 3H), 1.38 (t, J=7 Hz, 3H), 1.36 (d, J=7 Hz, 6H). ESI-LCMS m/z 575 (M+H)+.

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with 3:7 ethyl acetate

Sources & evidence

ORD record
ord-5075444de65a4cd29853d551db25715e
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

Loading…