(Trifluoromethyl)trimethylsilane → 1-(3-bromophenyl)-5-[(4-methoxybenzyl)oxy]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one

HRID 571077Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH:10]=[C:9]2[CH:25]=[O:26])[CH:5]=[CH:6][CH:7]=1.[F:27][C:28]([Si](C)(C)C)([F:30])[F:29].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH:10]=[C:9]2[CH:25]([OH:26])[C:28]([F:30])([F:29])[F:27])[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a semi-suspension of 1-(3-bromophenyl)-5-[(4-methoxybenzyl)oxy]-4-oxo-1,4-dihydropyridine-2-carbaldehyde (500 mg, 1.21 mmol) in THF (5 mL) at 0° C. was added (trifluoromethyl)trimethylsilane solution (5.3 mL of 0.5 mL solution in THF) followed by tetrabutylammonium fluoride solution (0.1 mL of a 1 M solution in THF). The reaction mixture was stirred at 0° C. for 1 h and then quenched by adding water. The quenched reaction mixture was then diluted with dichloromethane, washed with brine (1×), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography (24 g silica gel, linear gradient of 0 to 5% methanol in dichloromethane) afforded 1-(3-bromophenyl)-5-[(4-methoxybenzyl)oxy]-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one.

Workup

customquenched
additionby adding water
customThe quenched reaction mixture
washwashed with brine (1×)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash chromatography (24 g silica gel, linear gradient of 0 to 5% methanol in dichloromethane)

Sources & evidence

ORD record: ord-80889ce505c649c28456affedc569ef8
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09024032B2

Reaction notes

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