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

HRID 1278518Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1278518
[H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10]([C@H:12]1[C@H:17]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:16][C:15](=O)[N:14]([CH3:26])[C:13]1=O)=O)C.C1(C)C=CC=CC=1.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1COCC1.O>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C@@H:17]2[CH2:16][CH2:15][N:14]([CH3:26])[CH2:13][C@H:12]2[CH2:10][OH:9])=[CH:19][CH:20]=1

Komponenten

8

Edukt 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 15405466trans-3-Ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dioneHCID 21226445Aluminium lithium hydride

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 22635083Tetrahydrofuran tolueneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-2aa132d7e98c4a0ea35b10fc28db711d
Quelldatensatz
uspto-grants-2002_09
Patentnummer
US06444190B2

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