Reaction #1365699

Reaction equation

Water

NaOH

H2O

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

toluene

→

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

Solvents

toluene THF

THF

Conditions

Workup

1. 1
   workup.ADDITIONAfter addition
2. 2
   Otherreaction
3. 3
   Temperaturethe reaction was heated to >40° C. for 2 hr
4. 4
   TemperatureThe reaction was then cooled to <5° C.
5. 5
   Otherthe temperature below 15° C
6. 6
   OtherThe solid inorganic salts were removed by filtration
7. 7
   WashThese solids were washed with additional THF or toluene
8. 8
   ConcentrationThe filtered solution was then concentrated

Procedure

To a cooled solution of NaAlH4 (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, reaction was allowed to warm to room temperature. After 30 minutes at room temperature, the reaction was heated to >40° C. for 2 hr. The 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 were 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 lower yield (but 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.

Source