反应 #83939

反应方程式

fumaric acid

NH4Cl

methylmagnesium bromide

ethyl 3-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl]propionate

→

desired compound

收率 45.7%

4-[4-(6-Fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl]-2-methyl-2-hydroxybutane hemifumarate

收率 45.7%

溶剂

EtOAc

ether

H2O

EtOAc

THF

反应条件

后处理

1. 1
   温度with cooling
2. 2
   其他5.0 g of a fumarate salt was collected
3. 3
   其他The crude salt was recrystallized from MeOH

实验过程

To a stirred solution, under N2, of ethyl 3-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl]propionate (3.1 g, 9 mmol), in THF (100 ml) was added, dropwise, methylmagnesium bromide (9.0 ml, 27 mmol of a 3M solution in ether). The reaction was stirred at ambient temperature for 16 hours and then a saturated solution NH4Cl was added dropwise, with cooling. The reaction was further diluted with H2O, and after extractive workup of the aqueous mixture with EtOAc, 2.8 g of a waxy solid resulted. The solid was dissolved in EtOAc and 3.0 g of fumaric acid was added, and 5.0 g of a fumarate salt was collected, which was contaminated with unreacted fumaric acid. The crude salt was recrystallized from MeOH--Et2O, and then from DMF to afford 1.6 g (45.7%) of the desired compound as a hemifumarate, m.p.=237°-239° C.

来源