Hydrochloric Acid → 6-[4-({[5-Cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid

HRID 2423415Notes

Reaction equation

HRID 2423415 reaction equation
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[N:32]=[C:31]([C:36]([O:38]C)=[O:37])[CH:30]=[CH:29]4)=[CH:22][CH:21]=2)[CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>C(OCC)(=O)C.CO>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[N:32]=[C:31]([C:36]([OH:38])=[O:37])[CH:30]=[CH:29]4)=[CH:24][CH:25]=2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321529Methyl 6-[4-({[5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

Product 1

HCID 593215116-[4-({[5-Cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acidYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 6-[4-({[5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (67 mg, 0.12 mmol) in 2:1 tetrahydrofuran:methanol (1.5 mL) was added 1 N sodium hydroxide (0.18 mL, 0.18 mmol). The solution was heated in a microwave reactor at 120° C. for 500 seconds. The solution was concentrated and water was added followed by 1 N hydrochloric acid (0.18 mL, 0.18 mmol). Ethyl acetate was added. The layers were separated and the aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and concentrated to afford of 6-[4-({[5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid as a solid (51 mg, 78%). 1H-NMR (400 MHz, DMSO-d6) δ 13.38 (br s, 1H), 8.52 (d, J=8 Hz, 1H), 8.27 (s, 1H), 8.15-8.08 (m, 3H), 7.73 (d, J=9 Hz, 2H), 7.62-7.51 (m, 3H), 6.92 (d, J=9 Hz, 2H), 4.84 (s, 2H), 4.07-3.94 (m, 1H), 2.43-2.33 (m, 4H), 2.11-2.03 (m, 1H), 1.94-1.90 (m, 1H). HRMS (ESI) C30H22Cl2N2O4 calculated: 545.1029 (M+H)+, found: 545.1026 (M+H)+.

Workup

  1. concentrationThe solution was concentrated
  2. additionwater was added
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic layers were washed with brine
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-114f2132815344fab80a7b719552ab05
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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