Formaldehyde → (RS)-6-Benzyloxy-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-3,4-dihydro-2H-naphthalen-1-one

HRID 278454Notes

Reaction equation

HRID 278454 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])[CH2:14][CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:21][C:22]1[CH:35]=[CH:34][C:25]([CH2:26][C:27]2([OH:33])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:24][CH:23]=1.[CH2:36]=O>CN(C=O)C>[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]([CH2:36][N:30]1[CH2:29][CH2:28][C:27]([OH:33])([CH2:26][C:25]3[CH:24]=[CH:23][C:22]([CH3:21])=[CH:35][CH:34]=3)[CH2:32][CH2:31]1)[CH2:13][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 106822416-(benzyloxy)-3,4-dihydronaphthalen-1(2H)-oneHCID 226283764-[(4-Methylphenyl)methyl]piperidin-4-ol hydrochloride

Product 1

HCID 22628340(RS)-6-Benzyloxy-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-3,4-dihydro-2H-naphthalen-1-oneYield 57.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Benzyloxy-1-tetralone (1.26 g, 5 mmol), 4-(4-methyl-benzyl)-piperidin-4-ol hydrochloride (1.20 g, 5 mmol) and paraformaldehyde (150 mg, 5 mmol) in DMF (10 ml) were heated at 70° C. for 17 hr. The crude mixture was partitioned between distilled H2O (150 ml), 25% NH4OH (2 ml) and EtOAc (100 ml). The aqueous phase was further extracted with EtOAc (100 ml) and the combined organic extracts washed twice with satd NaCl solution (100 ml), dried Na2SO4 filtered and evaporated to afford an orange oil. Chromatography over SiO2 (Merck 230-400 mesh) eluting with EtOAc-Et3N (19:1) afforded (RS)-6-benzyloxy-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-3,4-dihydro-2H-naphthalen-1-one as an amber oil (1.34 g, 2.85 ml, 57%), MS m/e=470.3 (M+H+).

Workup

  1. customThe crude mixture was partitioned
  2. distillationbetween distilled H2O (150 ml), 25% NH4OH (2 ml) and EtOAc (100 ml)
  3. extractionThe aqueous phase was further extracted with EtOAc (100 ml)
  4. washthe combined organic extracts washed twice with satd NaCl solution (100 ml), dried Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford an orange oil
  8. washChromatography over SiO2 (Merck 230-400 mesh) eluting with EtOAc-Et3N (19:1)

Sources & evidence

ORD record
ord-ddd1b9777a1d4ca5a5ff29bb3a2f9d37
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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