Water → (-)-trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

HRID 1278519Notes

Reaction equation

HRID 1278519 reaction equation
C([O:3][C:4]([C@H:6]1[C@H:11]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:10][C:9](=O)[N:8]([CH3:20])[C:7]1=O)=O)C.C1(C)C=CC=CC=1.O.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1COCC1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C@@H:11]2[CH2:10][CH2:9][N:8]([CH3:20])[CH2:7][C@H:6]2[CH2:4][OH:3])=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 1140TolueneHCID 14798Sodium HydroxideHCID 15405466trans-3-Ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dione

Product 1

HCID 2734218(-)-trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

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.

Workup

  1. temperatureTo a cooled 50
  2. additionAfter addition
  3. customAfter 30 minutes at room temperature reaction
  4. temperatureis heated to >40° C. for 2 hr
  5. customReaction
  6. temperatureis then cooled to <5° C.
  7. customthe temperature below 15° C
  8. customThe solid inorganic salts are removed by filtration
  9. washThese solids are washed with additional THF or toluene
  10. concentrationThe filtered solution is then concentrated

Sources & evidence

ORD record
ord-8f1d3daf16334d058f3f2e5078148b13
Source dataset
uspto-grants-2002_09
Patent number
US06444190B2

Reaction notes

Loading…