2-Iodoxybenzoic acid → 3-(Cyclopropanecarbonyl)benzonitrile

HRID 1044826Notes

Reaction equation

I(C1C=CC=CC=1C(O)=O)(=O)=O.[CH:13]1([CH:16]([OH:25])[C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[C:20]#[N:21])[CH2:15][CH2:14]1>CCOC(C)=O>[CH:13]1([C:16]([C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[C:20]#[N:21])=[O:25])[CH2:15][CH2:14]1

Participants

Conditions

Temperature: 80 °C

Procedure

The key intermediate 3-(Cyclopropanecarbonyl)benzonitrile was prepared as follows; a) Cyclopropylmagnesium bromide (1M in THF, 6 ml, 6 mmol) was added to a solution of 3-formylbenzonitrile in THF (12 ml) at −78° C. and stirred at 0° C. for 5 hours. The reaction was quenched with saturated NH4Cl solution (30 ml), extracted with EtOAc, washed with water (×2) and brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica (EtOAc/Hexanes 20/80-50/50) to give 3-(cyclopropyl(hydroxy)methyl)benzonitrile (778 mg, 91%). b) 2-Iodoxybenzoic acid (IBX) was added to a solution of 3-(cyclopropyl(hydroxy)methyl)benzonitrile (171 mg, 1 mmol) in EtOAc (5 ml) at room temperature and stirred at 80° C. for 2 hours. After cooling to 0° C., the precipitated materials were filtered off and washed with EtOAc (3 ml×2), then the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica (EtOAc/Hexanes 5/95-30/70) to give 3-(cyclopropanecarbonyl)benzonitrile (225 mg, 100%).

Workup

temperatureAfter cooling to 0° C.
filtrationthe precipitated materials were filtered off
washwashed with EtOAc (3 ml×2)
customthe filtrate was evaporated under reduced pressure
customThe residue was purified by column chromatography on silica (EtOAc/Hexanes 5/95-30/70)

Sources & evidence

ORD record: ord-7706997eaa8043a2a6b90bc7478f8410
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563732B2

Reaction notes

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