HCID 58123623, compound → HCID 58123571, compound

HRID 536672Notes

Reaction equation

HRID 536672 reaction equation
[CH3:1][C:2]12[C:10]([CH3:12])([CH3:11])[CH:6]([NH:7][CH2:8][CH2:9]1)[CH2:5][C:4]1[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:3]2=1>CC(C)=O>[CH3:1][C:2]12[C:10]([CH3:11])([CH3:12])[CH:6]([NH:7][CH2:8][CH2:9]1)[CH2:5][C:4]1[CH:3]=[CH:16][CH:15]=[C:14]([OH:17])[C:13]2=1.[CH3:12][C:10]1([CH3:11])[CH2:6][NH:7][CH:8]2[CH2:5][C:4]3[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:3]=3[CH:9]2[CH:2]1[CH3:1]

Participants

4

Reactant 1

HCID 58123623HCID 58123623, compound

Product 2

HCID 58123571HCID 58123571, compoundHCID 58375174HCID 58375174, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

2-(3-Methoxy-benzyl)-3,3-dimethyl-4-methylene-piperidine-1-carbaldehyde (for preparation see J. Med. Chem. 1997, 40, 2928-2939; 47.5 g) is combined with 48% HBr in water (300 mL). The mixture is heated to reflux temperature and stirred at this temperature for 24 h. After cooling to ambient temperature, the precipitate is separated by filtration, washed with water, and triturated with acetone. Then, the precipitate is taken up in a mixture of 1 N aqueous NaOH solution and CH2Cl2. The CH2Cl2 phase is separated, dried (Na2SO4), and concentrated. The residue is recrystallized from EtOAc to afford 6,11,11-trimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-9-ol. The filtrate of the reaction mixture is combined with the water and acetone phases (from washing and triturating the precipitate) and basified using concentrated aqueous ammonia solution. The resulting mixture is extracted with CH2Cl2, the combined organic extracts are dried (MgSO4), and the solvent is evaporated. The residue is purified by chromatography on silica gel (EtOAc/MeOH/NH4OH 90:10:1->70:30:3) to afford 6,11,11-trimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-7-ol and 3,3,4-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-7-ol separated.

Workup

  1. washfrom washing
  2. customtriturating the precipitate) and
  3. extractionThe resulting mixture is extracted with CH2Cl2
  4. dry with materialthe combined organic extracts are dried (MgSO4)
  5. customthe solvent is evaporated
  6. customThe residue is purified by chromatography on silica gel (EtOAc/MeOH/NH4OH 90:10:1->70:30:3)

Sources & evidence

ORD record
ord-52366f7d42a94d5a9dcd5a4acf7c8d34
Source dataset
uspto-grants-2014_10
Patent number
US08859580B2

Reaction notes

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