N-Iodosuccinimide → Ethyl 4-iodo-3-(pyridin-2-yl)isoxazole-5-carboxylate

HRID 1506445Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[O:9][N:8]=1.[I:17]N1C(=O)CCC1=O>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[I:17][C:11]1[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[N:8][O:9][C:10]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

Conditions

Temperature: 120 °C

Procedure

A suspension of ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate (Preparation 63B, 6.25 g, 28.6 mmol), Palladium(II) acetate (1.61 g, 7.16 mmol) and 1-iodopyrrolidine-2,5-dione (12.9 g, 57.3 mmol) in acetonitrile (20 mL) was heated in the microwave for 30 minutes at 120° C. LC/MS analysis indicated that approximately 50% conversion had occurred. Additional 1-iodopyrrolidine-2,5-dione (12.9 g, 57.3 mmol) was added, and the reaction mixture heated for an additional 30 min. at 120° C. The reaction mixture was diluted with acetonitrile (25 mL) and filtered through a plug of Celite. The filtrate was concentrated and purified by silica gel column chromatography using an ISCO setup to afford ethyl 4-iodo-3-(pyridin-2-yl)isoxazole-5-carboxylate (4.00 g, 11.6 mmol, 41%). 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (t, 3H), 4.51 (q, J=7.04 Hz, 2H), 7.44 (ddd, J=7.48, 4.84, 1.32 Hz, 1H), 7.82-7.88 (m, 1H), 7.89-7.94 (m, 1H), and 8.81 (ddd, J=4.18, 1.32, 1.10 Hz, 1H).

Workup

temperaturethe reaction mixture heated for an additional 30 min. at 120° C
filtrationfiltered through a plug of Celite
concentrationThe filtrate was concentrated
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-e0840d7bf53c4ea5ac89454c97a814d1
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216972B2

Reaction notes

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