반응 #1365700

반응 방정식

NaOH

LiAlH4

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

toluene

→

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

용매

toluene THF

THF

H2O

Water

반응 조건

후처리

1. 1
   workup.ADDITIONAfter addition
2. 2
   기타After 30 minutes at room temperature reaction
3. 3
   온도was heated to >40° C. for 2 hr
4. 4
   기타Reaction
5. 5
   온도was then cooled to <5° C.
6. 6
   기타the temperature below 15° C
7. 7
   기타The solid inorganic salts were removed by filtration
8. 8
   세척These solids were washed with additional THF or toluene
9. 9
   농축The filtered solution was then concentrated

실험 절차

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.

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