反応 #1365701

反応方程式

toluene

H2O

NaOH

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

Water

→

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

溶媒

toluene THF

THF

反応条件

後処理

1. 1
   温度To a cooled 50
2. 2
   workup.ADDITIONAfter addition
3. 3
   その他After 30 minutes at room temperature reaction
4. 4
   温度is heated to >40° C. for 2 hr
5. 5
   その他Reaction
6. 6
   温度is then cooled to <5° C.
7. 7
   その他the temperature below 15° C
8. 8
   その他The solid inorganic salts are removed by filtration
9. 9
   洗浄These solids are washed with additional THF or toluene
10. 10
    濃縮The filtered solution is then concentrated

実験手順

To a cooled 50:50 mole mixture of NaAlH4/LiAlH4 (0.22 mol) in toluene/THF under argon is 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 is complete, the reaction is allowed to warm to room temperature. After 30 minutes at room temperature reaction is heated to >40° C. for 2 hr. 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