反応 #1365702

反応方程式

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

LiCl

Water

LiCl

NaOH

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

H2O

→

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

溶媒

THF

THF

toluene

toluene

反応条件

後処理

1. 1
   その他the temperature below 15° C
2. 2
   workup.ADDITIONAfter addition
3. 3
   その他reaction
4. 4
   温度the reaction is heated to >40° C. for 2 hr
5. 5
   温度The reaction is then cooled to <5° C.
6. 6
   その他the temperature below 15° C
7. 7
   その他The solid inorganic salts are removed by filtration
8. 8
   洗浄These solids are washed with additional THF or toluene
9. 9
   濃縮The filtered solution is then concentrated

実験手順

To a cooled mixture of NaAlH4 (0.22 mol) in toluene is added LiCl (0.11 mol) in THF. Note: LiCl can be added to the reactor prior to the addition of NaAlH4 or after the addition of the substrate, (+/−)trans 3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione. Next, (+/−)trans 3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione (0.083 mol) is added in THF (65 ml) holding the temperature below 15° C. After addition is completed, reaction is allowed to warm to room temperature. After 30 minutes at room temperature, the reaction is heated to >40° C. for 2 hr. The reaction is then cooled to <5° C. and toluene (50 ml) is added. Water (9 ml) is then added slowly holding the temperature below 15° C. Additional H2O or aqueous NaOH is used as necessary. The solid inorganic salts are removed by filtration. These solids are washed with additional THF or toluene. The filtered solution is then concentrated to give (+/−) trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine in essentially the same yield and 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.

出典