تفاعل #322632

معادلة التفاعل

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

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

K2CO3

fumaric acid

→

white solid

المردود 69.1%

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

المردود 69.1%

المذيبات

H2O

CH3CN

EtOAc

H2O

acetone

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةrefluxed for 4.5 hours
2. 2
   أخرىyielded 6.8 g of a partially solidified oil
3. 3
   أخرىThe product was purified by flash chromatography on silica gel
4. 4
   غسيلeluting the column with CH2Cl2
5. 5
   أخرىConcentration of the appropriate fractions yielded 5.2 g of a waxy solid
6. 6
   أخرىthe reaction
7. 7
   درجة الحرارةbriefly heated
8. 8
   درجة الحرارةat reflux
9. 9
   أخرىThe resultant fumarate salt precipitated from solution

الإجراء التجريبي

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.

المصدر