Hydrochloric Acid → 7-(4-{[(5-Cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylic acid

HRID 2423457Notes

Reaction equation

HRID 2423457 reaction equation
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11][C:12]3[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:19])[C:6]=2[CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:37]=[C:36]4[C:31]([CH:32]=[C:33]([C:38]([O:40]C)=[O:39])[N:34]=[CH:35]4)=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)[CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>CO>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([CH2:10][O:11][C:12]3[C:13]([CH3:19])=[CH:14][CH:15]=[CH:16][C:17]=3[CH3:18])[C:6]=2[CH2:20][O:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:37]=[C:36]4[C:31]([CH:32]=[C:33]([C:38]([OH:40])=[O:39])[N:34]=[CH:35]4)=[CH:30][CH:29]=3)=[CH:26][CH:27]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321545Methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylate

Product 1

HCID 593214847-(4-{[(5-Cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylic acidYield 84.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylate (50 mg, 0.091 mmol) in 2:1 tetrahydrofuran:methanol (3 mL) was added 1 N sodium hydroxide (0.14 mL, 0.14 mmol). The solution was heated in a microwave reactor at 100° C. for 500 seconds. Then 1 N hydrochloric acid (0.14 mL, 0.14 mmol) was added and the mixture was concentrated. The residue was taken up with ethyl acetate and water. The layers were separated and the organic layer was washed with water, dried over magnesium sulfate and concentrated to afford 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylic acid (41 mg, 84%). 1H-NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.61 (s, 1H), 8.49 (s, 1H), 8.24-8.18 (m, 2H), 7.85 (d, J=9 Hz, 2H), 7.16 (d, J=9 Hz, 2H), 7.00-6.90 (m, 3H), 5.06 (s, 2H), 4.90 (s, 2H), 4.01-3.90 (m, 1H), 2.39-2.30 (m, 4H), 2.14 (s, 6H), 2.10-2.00 (m, 1H), 1.90-1.89 (m, 1H). HRMS (ESI) C33H30N2O5 calculated: 535.2228 (M+H)+, found: 535.2228 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated
  2. customThe layers were separated
  3. washthe organic layer was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-79e5ba80a50344609602fa04e8c24274
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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