Hydrogen Bromide → HCID 58123623, compound

HRID 536671Notes

Reaction equation

HRID 536671 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[CH2:6][CH:7]1[C:12]([CH3:14])([CH3:13])[C:11](=[CH2:15])[CH2:10][CH2:9][N:8]1C=O.Br>O>[CH3:15][C:11]12[C:12]([CH3:13])([CH3:14])[CH:7]([NH:8][CH2:9][CH2:10]1)[CH2:6][C:5]1[CH:4]=[C:3]([OH:2])[CH:20]=[CH:19][C:18]2=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 10492506HCID 10492506, compound

Product 1

HCID 58123623HCID 58123623, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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. temperatureThe mixture is heated
  2. temperatureto reflux temperature
  3. customthe precipitate is separated by filtration
  4. washwashed with water
  5. customtriturated with acetone
  6. additionThen, the precipitate is taken up in a mixture of 1 N aqueous NaOH solution and CH2Cl2
  7. customThe CH2Cl2 phase is separated
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe residue is recrystallized from EtOAc

Sources & evidence

ORD record
ord-821af4c7e195406caa0dfc9cb519ec5a
Source dataset
uspto-grants-2014_10
Patent number
US08859580B2

Reaction notes

Loading…