反応 #1365700

反応方程式

NaOH

LiAlH4

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

toluene

→

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

溶媒

toluene THF

THF

H2O

Water

反応条件

後処理

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

実験手順

To a cooled solution of LiAlH4 (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, the reaction was allowed to warm to room temperature. After 30 minutes at room temperature reaction was heated to >40° C. for 2 hr. 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 was 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 higher yield (but similar impurity profile) as with NaAlH4 as shown by HPLC analysis. The product can be recovered by standard procedures such as trituration with a less polar solvent.

出典