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

HRID 646017Notes

Reaction equation

HRID 646017 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]1[C:14]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[C:29]([C:33]([O:35]CC)=[O:34])=[CH:28][CH:27]=[CH:26]4)=[CH:19][CH:18]=2)=[C:13]([CH:38]([CH3:40])[CH3:39])[O:12][N:11]=1.C(O)C.[OH-].[Na+].Cl>O1CCCC1>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[CH2:9][C:10]1[C:14]([CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[C:29]([C:33]([OH:35])=[O:34])=[CH:28][CH:27]=[CH:26]4)=[CH:21][CH:22]=2)=[C:13]([CH:38]([CH3:40])[CH3:39])[O:12][N:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14798Sodium Hydroxide2×HCID 59264872HCID 59264872, compound

Product 1

HCID 247390196-[4-({[3-[(2,6-Dichlorophenyl)methyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylic acidYield 102.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution of ethyl 6-[4-({[3-[(2,6-dichlorophenyl)methyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate (0.116 g, 0.20 mmol) in tetrahydrofuran (2 mL) was placed in a microwave reaction tube. Ethanol (1 mL) was added followed by 1N sodium hydroxide (0.312 mL, 0.31 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 with 1 N hydrochloric acid and concentrated. The residue was slurried in hexanes. The solid was slurried in water and the mixture was decanted and the solid dried to yield the title compound as a white solid (0.112 g, 100% as 0.15EtOAc). 1H NMR (DMSO-d6) δ 13.14 (s, 1H), 8.91 (d, J=9 Hz, 1H), 8.26 (s, 1H), 8.20 (d, J=8 Hz, 1H), 8.10 (d, J=7 Hz, 1H), 7.96 (dd, J=2, 9 Hz, 1H), 7.80 (d, J=9 Hz, 2H), 7.58 (m, 1H), 7.46 (d, J=8 Hz, 2H), 7.31 (t, J=8 Hz, 1H), 7.16 (d, J=9 Hz, 2H), 5.08 (s, 2H), 4.29 (s, 2H), 3.36 (septet, J=7 Hz, overlapping H2O 1H), 1.22 (d, J=7 Hz, 6H). HRMS C31H25NO4Cl2 m/z 546.1239 (M+H)+Cal; 546.1226 (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 mixture was decanted
  5. customthe solid dried

Sources & evidence

ORD record
ord-25a2f771bbff441cbd699538e16814a3
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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