Hydrochloric Acid → Ethyl 4-cyano-7-hydroxy-3-(4-methoxyphenyl)isoxazolo[4,5-c]pyridine-6-carboxylate

HRID 2388214Notes

Reaction equation

[OH:1][C:2]1[C:3]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:4]=2[C:5](I)=[N:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[C:25]([Cu])#[N:26].[OH-].[NH4+].Cl>CCOC(C)=O.CN1CCCC1=O>[C:25]([C:5]1[C:4]2[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[N:15][O:16][C:3]=2[C:2]([OH:1])=[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1)#[N:26]

Participants

Conditions

Temperature: 110 °C

Procedure

Ethyl 7-hydroxy-4-iodo-3-(4-methoxyphenyl)isoxazolo[4,5-c]pyridine-6-carboxylate (390 mg, 0.89 mmol) and CuCN (238 mg, 2.66 mmol) were added to 6 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 (100 mL, 30% aqueous solution) and EtOAc (100 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 178 mg of the title compound. MS: (+) m/z 340.42 (M+1).

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-2a357806c34b48139b82cb0a1d0c22f3
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08269008B2

Reaction notes

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