Hydrochloric Acid → 5-Cyclopropyl-3-(3,5-dichloro-4-pyridyl)isoxazole-4-carboxylic Acid

HRID 2423431Notes

Reaction equation

HRID 2423431 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][N:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[C:17]([O:19]CC)=[O:18])[CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>CO>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][N:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[C:17]([OH:19])=[O:18])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321466Ethyl 5-Cyclopropyl-3-(3,5-dichloro-4-pyridyl)isoxazole-4-carboxylate

Product 1

HCID 593215165-Cyclopropyl-3-(3,5-dichloro-4-pyridyl)isoxazole-4-carboxylic AcidYield 82.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of ethyl 5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylate (210 mg, 0.642 mmol) in 2:1 tetrahydrofuran:methanol (3 mL) was added 1 N sodium hydroxide (0.963 mL, 0.963 mmol). The solution was heated in a microwave reactor to 120° C. for 500 seconds. Then 1 N hydrochloric acid (0.963 mL, 0.963 mmol) was added and the solution was concentrated. The residue was taken up with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated to afford 5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid (158 mg, 82%). 1H-NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 8.81 (s, 2H), 2.91-2.84 (m, 1H), 1.34-1.24 (m, 4H).

Workup

  1. concentrationthe solution was concentrated
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c8001ca8f47e4c3a9c852d6f4bc8d530
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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