Hydrochloric Acid → Ethyl 3-(5-bromofuran-2-yl)-4-cyano-7-hydroxyisoxazolo[4,5-c]pyridine-6-carboxylate

HRID 2388216Notes

Reaction equation

[Br:1][C:2]1[O:6][C:5]([C:7]2[C:11]3[C:12](I)=[N:13][C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:15]([OH:16])[C:10]=3[O:9][N:8]=2)=[CH:4][CH:3]=1.[C:23]([Cu])#[N:24].[OH-].[NH4+].Cl>CCOC(C)=O.CN1CCCC1=O>[Br:1][C:2]1[O:6][C:5]([C:7]2[C:11]3[C:12]([C:23]#[N:24])=[N:13][C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:15]([OH:16])[C:10]=3[O:9][N:8]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Ethyl 3-(5-bromofuran-2-yl)-7-hydroxy-4-iodoisoxazolo[4,5-c]pyridine-6-carboxylate (155 mg, 0.324 mmol) and CuCN (87 mg, 0.971 mmol) were added to 2.2 mL of N-methyl-2-pyrrolidone. The resulting suspension was heated in an oil bath (T=110° C.) for 1 h. The reaction mixture was cooled slightly and poured into a vigorously stirring mixture of ammonium hydroxide (5 mL, 15% aqueous solution) and EtOAc (50 mL). The mixture was acidified with concentrated hydrochloric acid to pH 3 and extracted with EtOAc. The combined organic layer was dried over MgSO4 and concentrated, and the residue was purified flash chromatography (0-100% EtOAc/hexanes) to afford 42 mg of the title compound. MS: (+) m/z 378.29, 380.26 (M+1, 79Br/81Br).

Workup

temperatureThe reaction mixture was cooled slightly
additionpoured into
extractionextracted with EtOAc
dry with materialThe combined organic layer was dried over MgSO4
concentrationconcentrated
customthe residue was purified flash chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-fad87598b1514d5b8864430f50e5af47
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08269008B2

Reaction notes

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