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

HRID 1199803Notes

Reaction equation

HRID 1199803 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.[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1>C1(C)C=CC=CC=1.O1CCCC1.C1(C)C=CC=CC=1>[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

6

Reactant 3

HCID 8028TetrahydrofuranHCID 15405466trans-3-Ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dioneHCID 21226445Aluminium lithium hydride2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

Compound E4 (34 g) in toluene (150 ml) was added slowly to a slurry of lithium aluminium hydride (10 g) in a tetrahydrofuran (50 ml)/toluene (150 ml) mixture, maintaining the temperature at 0°-5° C. under nitrogen. (Commercially available solutions of lithium aluminium hydride in tetrahydrofuran/toluene have also been used successfully). The mixture was stirred for a further 1-5 hours and then allowed to warm up to 15°-25° C. overnight. The excess lithium aluminium hydride was destroyed by the carefully controlled addition of water (10 ml), dilute 15% sodium hydroxide (10 mls) and water (30 ml). The solids were then removed by filtration and reslurried in toluene (100 ml). The combined rich toluene layers were concentrated to a low volume (75 ml) and poured into petroleum ether [100°-120°] (25 ml). After stirring for 8-24 hours the product was isolated by filtration, washed with petroleum ether (10 ml) and dried.

Workup

  1. temperaturemaintaining the temperature at 0°-5° C. under nitrogen
  2. temperatureto warm up to 15°-25° C. overnight
  3. customThe excess lithium aluminium hydride was destroyed by the carefully controlled addition of water (10 ml)
  4. additiondilute 15% sodium hydroxide (10 mls) and water (30 ml)
  5. customThe solids were then removed by filtration
  6. concentrationThe combined rich toluene layers were concentrated to a low volume (75 ml)
  7. additionpoured into petroleum ether [100°-120°] (25 ml)
  8. stirringAfter stirring for 8-24 hours the product
  9. customwas isolated by filtration
  10. washwashed with petroleum ether (10 ml)
  11. customdried

Sources & evidence

ORD record
ord-97683df782fb4584b10a945fbf0908d7
Source dataset
uspto-grants-1990_02
Patent number
US04902801

Reaction notes

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