Ethanol → 6-[4-({[3-[2-(2,6-Dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylic acid

HRID 1693667Notes

Reaction equation

HRID 1693667 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][CH2:10][C:11]1[C:15]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[C:30]([C:34]([O:36]CC)=[O:35])=[CH:29][CH:28]=[CH:27]4)=[CH:20][CH:19]=2)=[C:14]([CH:39]([CH3:41])[CH3:40])[O:13][N:12]=1.C(O)C.[OH-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][CH2:10][C:11]1[C:15]([CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[C:30]([C:34]([OH:36])=[O:35])=[CH:29][CH:28]=[CH:27]4)=[CH:22][CH:23]=2)=[C:14]([CH:39]([CH3:41])[CH3:40])[O:13][N:12]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium Hydroxide2×HCID 59264854Ethyl 6-[4-({[3-[2-(2,6-dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate

Product 1

HCID 247391696-[4-({[3-[2-(2,6-Dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylic acidYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution of ethyl 6-[4-({[3-[2-(2,6-dichlorophenyl)ethyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate (0.110 g, 0.187 mmol) in tetrahydrofuran (2 mL) was placed in a microwave reaction tube. Ethanol (1 mL) was added followed by 1 N sodium hydroxide (0.36 mL, 0.36 mmol). The tube was sealed and heated in a microwave reactor to 100° C. for 500 seconds. Additional sodium hydroxide solution (0.2 mL, 0.2 mmol) was added and the solution was heated in a microwave reactor to 100° C. for another 500 seconds. The solution was neutralized and concentrated. The residue was partitioned between water and ethyl acetate. The organic layer was concentrated to yield the title compound as a white solid (0.088 g, 83.8%). 1H NMR (DMSO-d6): 13.14 (s, 1H), 8.91 (d, J=9 Hz, 1H), 8.27 (d, J=1 Hz, 1H), 8.20 (d, J=8 Hz, 1H), 7.96 (dd, J=2, 9 Hz, 2H), 7.80 (d, J=9 Hz, 2H), 7.58 (m, 1H), 7.43 (d, J=8 Hz, 2H), 7.26 (m, 1H), 7.15 (d, J=9 Hz, 2H), 4.98 (s, 2H), 3.35 (septet, J=7 Hz, overlapping H2O, 1H), 3.25-3.20 (m, 2H), 2.89-2.85 (m, 2H), 1.25 (d, J=7 Hz, 6H). HRMS C32H27NO4Cl2 m/z 560.1395 (M+H)+Cal; 560.1409 (M+H)+Obs.

Workup

  1. customThe tube was sealed
  2. temperaturethe solution was heated in a microwave reactor to 100° C. for another 500 seconds
  3. concentrationconcentrated
  4. customThe residue was partitioned between water and ethyl acetate
  5. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-18ada50a72714d03be0f3a1c4f143d53
Source dataset
uspto-grants-2012_04
Patent number
US08158665B2

Reaction notes

Loading…