Sodium Hydroxide → (RS)-1-[(3SR,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanol

HRID 2191108Notes

Reaction equation

HRID 2191108 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:16])[CH3:15])[CH:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+].[O-]S([O-])(=O)=O.[Na+].[Na+]>C1COCC1.O.C1COCC1.O.C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([OH:16])[CH3:15])[CH:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 24436Sodium SulfateHCID 21226445Aluminium lithium hydrideHCID 684757041-[(3SR,4RS)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanone

Product 1

HCID 68475389(RS)-1-[(3SR,4SR)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanol

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

Under an inert atmosphere a 100 mL four necked flask (flame dried) with a magnetic stirrer was charged with 835 mg (2.54 mmol) 1-[(3SR,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanone in 25 mL THF. The yellow solution was cooled to 0° C. and 34 mg (0.89 mmol) LiAlH4 was added. The mixture was stirred for 30 min at 0° C. and 30 min from 0° C. to 15° C. At 0° C. 10 mL ethyl acetate was added drop-wise, followed by 5 mL THF:water 9:1 and 1 mL 4 N aqueous NaOH and 1 mL water. The mixture was stirred for 30 min at 40-50° C. and Na2SO4 was added. The mixture was filtered off and concentrated under vacuum. The residue was purified by chromatography on silica eluting with a gradient formed from DCM, methanol, NH3aq. to yield after evaporation of the product containing fractions 466 mg (55%) of the title compound as off-white foam. MS (m/e): 330.1 [(M+H)+].

Workup

  1. customAt 0° C
  2. stirringThe mixture was stirred for 30 min at 40-50° C.
  3. filtrationThe mixture was filtered off
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by chromatography on silica eluting with a gradient
  6. customformed from DCM, methanol, NH3aq
  7. customto yield
  8. customafter evaporation of the product
  9. additioncontaining fractions 466 mg (55%) of the title compound as off-white foam

Sources & evidence

ORD record
ord-a40bf94195b94a6bbdedc36a5b99bc64
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

Loading…