Reaktion #73891

Reaktionsgleichung

1H-Benzotriazolium

tetrafluoroborate

dimethylamine

methyl N-{(1R)-1-(2,4-difluorophenyl)-2-[(2-hydroxyphenyl)amino]-2-oxoethyl}-L-leucinate

1,1′-thiocarbonyldiimidazole

→

methyl N-[1-(2,4-difluorophenyl)-2-(dimethylamino)-2-oxoethyl]-L-leucinate

Ausbeute 58.5%

Lösungsmittel

tetrahydrofuran

dichloromethane

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture was stirred for a further 18 hours
2. 2
   Wascheneluting with a gradient (8:1 to 1:2 cyclohexane:ethyl acetate)
3. 3
   Sonstigeevaporated

Vorschrift

A solution of methyl N-{(1R)-1-(2,4-difluorophenyl)-2-[(2-hydroxyphenyl)amino]-2-oxoethyl}-L-leucinate (203 mg) and 1,1′-thiocarbonyldiimidazole (100 mg) in dichloromethane (5 ml) was left to stand for 18 hours. Water (10 l) was added to the reaction mixture and this was then stirred rapidly for 30 minutes. After this, 1H-Benzotriazolium, 1-[bis(dimethylamino)methylene]-, tetrafluoroborate (1-), 3-oxide (TBTU, 321 mg) and a solution of dimethylamine in tetrahydrofuran (0.5 ml of 2M solution) were added. The reaction mixture was stirred for a further 18 hours and was then passed down an SPE (5 g, silica) eluting with a gradient (8:1 to 1:2 cyclohexane:ethyl acetate). The required fractions were combined and evaporated to furnish methyl N-[1-(2,4-difluorophenyl)-2-(dimethylamino)-2-oxoethyl]-L-leucinate (100 mg).

Quelle