反应 #1857589

反应方程式

[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

溶剂

dichloromethane

dichloromethane

反应条件

后处理

1. 1
   其他The 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
   其他the aqueous phase was removed
5. 5
   萃取extracted with ethyl acetate
6. 6
   干燥The combined organic phases were dried over sodium sulphate
7. 7
   浓缩concentrated
8. 8
   其他Purification by column chromatography

实验过程

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).

来源