Hydrochloric Acid → 5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid

HRID 2423420Notes

Reaction equation

[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][N:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[C:18]([O:20]CC)=[O:19])[CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>CO>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:11]([Cl:17])=[CH:12][N:13]=[CH:14][C:15]=3[Cl:16])[C:6]=2[C:18]([OH:20])=[O:19])[CH2:2][CH2:3][CH2:4]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of ethyl 5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylate (1.00 g, 2.93 mmol), in 2:1 tetrahydrofuran:methanol (15 mL) was added 1 N aqueous sodium hydroxide (4.40 mL, 4.40 mmol). The solution was heated in a microwave reactor to 120° C. for 500 seconds. Then 1 N aqueous hydrochloric acid (4.40 mL, 4.40 mmol) was added and the solution was concentrated. Water was added and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, concentrated and dried under a nitrogen stream at 45° C. overnight to afford 5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl) -4-isoxazolecarboxylic acid (808 mg, 88%). 1H-NMR (400 MHz, DMSO-d6) δ 13.34 (br s, 1H), 8.81 (s, 2H), 4.33-4.25 (m, 1H), 2.42-2.32 (m, 4H), 2.15-2.05 (m, 1H), 1.96-1.88 (m, 1H).

Workup

concentrationthe solution was concentrated
additionWater was added
extractionthe mixture was extracted twice with ethyl acetate
washThe combined organic layers were washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customdried under a nitrogen stream at 45° C. overnight

Sources & evidence

ORD record: ord-bb22dc44e34047058028f05d7afe0d0f
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960552B2

Reaction notes

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