Imidazole → 4-((Tert-butyldimethylsilyl)oxy)-2-fluorobenzonitrile

HRID 1873941Notes

Reaction equation

[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].N1C=CN=C1.[CH3:16][C:17]([Si:20](Cl)([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C=O)C>[Si:20]([O:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1)([C:17]([CH3:19])([CH3:18])[CH3:16])([CH3:22])[CH3:21]

Participants

Conditions

Temperature: 0 °C

Procedure

2-Fluoro-4-hydroxybenzonitrile (30.1 g; manufactured by Wako Pure Chemical Industries, Ltd.) and imidazole (18.3 g; manufactured by Tokyo Chemical Industry Co., Ltd.) were dissolved in dehydrated DMF (436 mL; manufactured by Kanto Chemical Co., Inc.). After cooling to 0° C., TBDMSCl (48.3 g; manufactured by Tokyo Chemical Industry, Co., Ltd.) was added and the mixture was stirred for 1 hour while warming to room temperature. Solvent contained in the reaction solution was evaporated under reduced pressure. After adding water, extraction was carried out twice with ethyl acetate. The organic layer was washed twice with water and brine and dried over anhydrous sodium sulfate. After the solvent was evaporated under reduced pressure, purification was carried out with column chromatography (“COLUMN-A”; n-hexane:ethyl acetate=100:0→94:6) to obtain the title compound (40.3 g).

Workup

temperaturewhile warming to room temperature
customwas evaporated under reduced pressure
additionAfter adding
extractionwater, extraction
washThe organic layer was washed twice with water and brine
dry with materialdried over anhydrous sodium sulfate
customAfter the solvent was evaporated under reduced pressure, purification

Sources & evidence

ORD record: ord-e885c661ccc449c48c8ee1ca1fa19b62
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304443B2

Reaction notes

Loading…