반응 #1857584

반응 방정식

[3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid

oxalyl chloride

sodium hydrogencarbonate

4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride

triethylamine

→

2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   기타The solvent and the excess reagent are removed under reduced pressure
2. 2
   workup.DISSOLUTIONThe solid residue is again dissolved in dichloromethane and, at 0° C.
3. 3
   workup.STIRRINGThe reaction mixture is stirred at room temperature overnight
4. 4
   기타the aqueous phase is removed
5. 5
   추출extracted with ethyl acetate
6. 6
   건조The combined organic phases are dried over sodium sulphate
7. 7
   농축concentrated
8. 8
   기타Purification by column chromatography

실험 절차

To a solution of [3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid (177 mg) in dichloromethane (40 ml) are added, at 0° C., oxalyl chloride (290 mg) and one drop of N,N-dimethylformamide. The reaction mixture is stirred at room temperature for 2 hours. The solvent and the excess reagent are removed under reduced pressure. The solid residue is again dissolved in dichloromethane and, at 0° C., added dropwise to a solution of 4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride and triethylamine (5.0 eq.) in dichloromethane (25 ml). The reaction mixture is stirred at room temperature overnight. Then it is admixed with concentrated sodium hydrogencarbonate solution, and the aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated. Purification by column chromatography gives 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (110 mg).

출처