反应 #1365699

反应方程式

Water

NaOH

H2O

(+/−) trans-3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione

toluene

→

(+/−) trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

溶剂

toluene THF

THF

反应条件

后处理

1. 1
   workup.ADDITIONAfter addition
2. 2
   其他reaction
3. 3
   温度the reaction was heated to >40° C. for 2 hr
4. 4
   温度The reaction was then cooled to <5° C.
5. 5
   其他the temperature below 15° C
6. 6
   其他The solid inorganic salts were removed by filtration
7. 7
   洗涤These solids were washed with additional THF or toluene
8. 8
   浓缩The filtered solution was then concentrated

实验过程

To a cooled solution of NaAlH4 (0.22 mol) in toluene/THF under argon was added (+/−) trans-3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione (0.083 mol) in THF holding the temperature below 15° C. After addition was complete, reaction was allowed to warm to room temperature. After 30 minutes at room temperature, the reaction was heated to >40° C. for 2 hr. The reaction was then cooled to <5° C. and toluene (50 ml) was added. Water (9 ml) was then added slowly holding the temperature below 15° C. Additional H2O or aqueous NaOH were used as necessary. The solid inorganic salts were removed by filtration. These solids were washed with additional THF or toluene. The filtered solution was then concentrated to give (+/−) trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine in lower yield (but similar impurity profile as with LiAlH4) as shown by HPLC analysis. The product can be recovered by standard procedures such as trituration with a less polar solvents.

来源