Water → (1RS,2RS)-1-(6-Benzyloxy-1-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol

HRID 278453Notes

Reaction equation

HRID 278453 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[CH:14]([CH2:20][N:21]1[CH2:26][CH2:25][C:24]([OH:35])([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)[CH2:23][CH2:22]1)[CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]([OH:19])[CH:14]([CH2:20][N:21]1[CH2:22][CH2:23][C:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)([OH:35])[CH2:25][CH2:26]1)[CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 22628340(RS)-6-Benzyloxy-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-3,4-dihydro-2H-naphthalen-1-one

Product 1

HCID 22628392(1RS,2RS)-1-(6-Benzyloxy-1-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-olYield 57.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(RS)-6-Benzyloxy-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-3,4-dihydro-2H-naphthalen-1-one (1.30 g, 2.77 mmol) in THF (15 ml) was added dropwise to a suspension of LiAlH4 (0.6 g, 15.5 mmol) in THF (20 ml) over 15 min (5-10° C.) and then stirred at RT for 2.5 hr. Distilled H2O (1 ml) and 4N NaOH (2 ml) followed by further H2O (2 ml), was added to quench the reaction and stirred vigorously 15 min., the mixture was then dried with Na2SO4, filtered and evaporated. The resulting crude liquid was chromatographed over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2—MeOH—NH4OH (100:5:0.25) to afford the title compound as a white foam (0.75 g, 1.6 mmol, 57%), MS m/e=472.4 (M+H+).

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. stirringstirred vigorously 15 min.
  5. dry with materialthe mixture was then dried with Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe resulting crude liquid was chromatographed over SiO2 (Merck 230-400 mesh)
  9. washeluting with CH2Cl2—MeOH—NH4OH (100:5:0.25)

Sources & evidence

ORD record
ord-076fd99e57d548c2b13c540975ab88a2
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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