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

HRID 646001Notes

Reaction equation

HRID 646001 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)[C:20]([C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:18]=[CH:17]3)=[CH:10][CH:9]=1.Cl[CH2:29][C:30]1[C:31]([C:38]2[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:45])=[N:32][O:33][C:34]=1[CH:35]([CH3:37])[CH3:36]>CN(C)C=O>[Cl:44][C:43]1[CH:42]=[CH:41][CH:40]=[C:39]([Cl:45])[C:38]=1[C:31]1[C:30]([CH2:29][O:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20]([C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:18]=[CH:17]4)=[CH:12][CH:13]=2)=[C:34]([CH:35]([CH3:37])[CH3:36])[O:33][N:32]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 59264867Methyl 6-(4-hydroxyphenyl)-1-naphthoateHCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazole

Product 1

HCID 59264878Methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylateYield 48.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

Cesium carbonate (352 g, 1.08 mol) was added to a mechanically stirred solution of methyl 6-(4-hydroxyphenyl)-1-naphthoate (199 g, 0.72 mol) in dimethylformamide (1 L) under N2. The resulting suspension was heated to 65° C. for 30 min followed by addition of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole (280 g, 0.92 mol) in dimethylformamide (500 mL). The mixture was heated at 65° C. for 18 h, cooled to room temperature and partitioned between ethyl acetate (1 L) and water (1 L). The ethyl acetate layer was backwashed with water (2×1 L) and concentrated to a thick black syrup. This syrup was triturated with hexane (500 mL) and ethyl acetate (300 mL) for 2 h. Filtration gave 190 g of the product as beige crystals. 1H NMR (DMSO-d6); δ 8.77 (d, J=9 Hz, 1H), 8.23-8.20 (m, 2H), 8.09 (d, J=7 Hz, 1H), 7.92 (dd, J=2, 9 Hz, 1H), 7.69 (d, J=9 Hz, 2H), 7.63-7.51 (m, 4H), 6.91 (d, J=9 Hz, 2H), 4.86 (s, 2H), 3.92 (s, 3H), 3.45 (septet, J=7 Hz, 1H), 1.33 (d, J=7 Hz, 6H). ESI-LCMS m/z 546 (M+H)+.

Workup

  1. temperatureThe mixture was heated at 65° C. for 18 h
  2. temperaturecooled to room temperature
  3. custompartitioned between ethyl acetate (1 L) and water (1 L)
  4. concentrationconcentrated to a thick black syrup
  5. customThis syrup was triturated with hexane (500 mL) and ethyl acetate (300 mL) for 2 h
  6. filtrationFiltration

Sources & evidence

ORD record
ord-9830022b36bc4587a06fdffc7da99aa7
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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