반응 #1857589

반응 방정식

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

oxalyl chloride

sodium hydrogencarbonate

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

triethylamine

→

2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-fluorobenzaldehyde

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   기타The solvent and the excess reagent were removed under reduced pressure
2. 2
   workup.DISSOLUTIONThe solid residue was again dissolved in dichloromethane (5 ml) and, at 0° C.
3. 3
   workup.STIRRINGThe reaction mixture was stirred at room temperature overnight
4. 4
   기타the aqueous phase was removed
5. 5
   추출extracted with ethyl acetate
6. 6
   건조The combined organic phases were 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 (58 mg) in dichloromethane (20 ml) were added, at 0° C., oxalyl chloride (94.5 mg) and one drop of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 2 hours. The solvent and the excess reagent were removed under reduced pressure. The solid residue was again dissolved in dichloromethane (5 ml) and, at 0° C., added dropwise to a solution of 4-{4-[5-(2-fluoro-6-formylphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride and triethylamine (5.0 eq.) in dichloromethane (15 ml). The reaction mixture was stirred at room temperature overnight. Then it was admixed with concentrated sodium hydrogencarbonate solution, and the aqueous phase was removed and extracted with ethyl acetate. The combined organic phases were dried over sodium sulphate and concentrated. Purification by column chromatography gave 2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-fluorobenzaldehyde (55 mg).

출처