반응 #1365701

반응 방정식

toluene

H2O

NaOH

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

Water

→

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

용매

toluene THF

THF

반응 조건

후처리

1. 1
   온도To a cooled 50
2. 2
   workup.ADDITIONAfter addition
3. 3
   기타After 30 minutes at room temperature reaction
4. 4
   온도is heated to >40° C. for 2 hr
5. 5
   기타Reaction
6. 6
   온도is then cooled to <5° C.
7. 7
   기타the temperature below 15° C
8. 8
   기타The solid inorganic salts are removed by filtration
9. 9
   세척These solids are washed with additional THF or toluene
10. 10
    농축The filtered solution is then concentrated

실험 절차

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.

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