反应 #351407

反应方程式

6-fluoro-3-(4-piperidinyl)-1,2-benzisothiazole

(R)-(-)-3-bromo-2-methyl-1-propanol

K2CO3

fumaric acid

→

white solid

收率 69.1%

(S)-6-Fluoro-3-[1-(3-hydroxy-2-methylpropyl)-4-piperidinyl]-1,2-benzisothiazole fumarate

收率 69.1%

溶剂

H2O

CH3CN

EtOAc

H2O

acetone

反应条件

后处理

1. 1
   温度refluxed for 4.5 hours
2. 2
   其他yielded 6.8 g of a partially solidified oil
3. 3
   其他The product was purified by flash chromatography on silica gel
4. 4
   洗涤eluting the column with CH2Cl2
5. 5
   其他Concentration of the appropriate fractions yielded 5.2 g of a waxy solid
6. 6
   其他the reaction
7. 7
   温度briefly heated
8. 8
   温度at reflux
9. 9
   其他The resultant fumarate salt precipitated from solution

实验过程

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisothiazole (4.6 g, 20 mmol), (R)-(-)-3-bromo-2-methyl-1-propanol (3.0 g, 20 mmol), K2CO3 (2.7 g, 20 mmol), tetrabutylammonium sulfate (0.058 g), CH3CN (95 ml) and H2O (19 ml) was stirred and refluxed for 4.5 hours. After standing at ambient temperature for 16 hours, the reaction was poured into H2O, and subsequent extractive workup of the aqueous with EtOAc yielded 6.8 g of a partially solidified oil. The product was purified by flash chromatography on silica gel, eluting the column with CH2Cl2, then 2% MeOH--CH2Cl2 and finally 5% MeOH--CH2Cl2. Concentration of the appropriate fractions yielded 5.2 g of a waxy solid. The solid was dissolved in acetone and fumaric acid (1.9 g, 1.0 eq) was added and the reaction briefly heated at reflux. The resultant fumarate salt precipitated from solution yielding 4.8 g of white solid. The compound was recrystallized from acetonitrile to yield 3.1 g (36%) of the alcohol as a white solid, m.p.=151°-153° C.

来源