تفاعل #1365702

معادلة التفاعل

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

LiCl

Water

LiCl

NaOH

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

H2O

→

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

المذيبات

THF

THF

toluene

toluene

ظروف التفاعل

المعالجة

1. 1
   أخرىthe temperature below 15° C
2. 2
   workup.ADDITIONAfter addition
3. 3
   أخرىreaction
4. 4
   درجة الحرارةthe reaction is heated to >40° C. for 2 hr
5. 5
   درجة الحرارةThe reaction is then cooled to <5° C.
6. 6
   أخرىthe temperature below 15° C
7. 7
   أخرىThe solid inorganic salts are removed by filtration
8. 8
   غسيلThese solids are washed with additional THF or toluene
9. 9
   تركيزThe filtered solution is then concentrated

الإجراء التجريبي

To a cooled mixture of NaAlH4 (0.22 mol) in toluene is added LiCl (0.11 mol) in THF. Note: LiCl can be added to the reactor prior to the addition of NaAlH4 or after the addition of the substrate, (+/−)trans 3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione. Next, (+/−)trans 3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione (0.083 mol) is added in THF (65 ml) holding the temperature below 15° C. After addition is completed, reaction is allowed to warm to room temperature. After 30 minutes at room temperature, the reaction is heated to >40° C. for 2 hr. The 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.

المصدر