Hydroxyamine hydrochloride → 2,8a-Dimethyl-4a-(3-methoxyphenyl)octahydroisoquinolin-6-one Oxime

HRID 1453970Notes

Reaction equation

HRID 1453970 reaction equation
[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[C:4]([CH3:21])([CH2:5][CH2:6][CH:7](O)[CH2:8]2)[CH:3]1C.Cl.[NH2:24][OH:25]>CCO>[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[C:4]([CH3:21])([CH2:5][CH2:6][C:7](=[N:24][OH:25])[CH2:8]2)[CH2:3]1

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 68831190n,8a-Dimethylmethyl-4a-(3-methoxyphenyl)octahydro-6-isoquinolinol

Product 1

HCID 729884842,8a-Dimethyl-4a-(3-methoxyphenyl)octahydroisoquinolin-6-one OximeYield 96.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-Methyl-4aβ-(3-methoxyphenyl)octahydro-6-oxadecahydroisoquinoline 17 (1.41 g, 4.9 mmol) and hydroxylamine hydrochloride (1.70 g, 24.5 mmol) in EtOH (absolute, 100 mL) were heated to reflux for 5 h. The reaction mixture was allowed to cool to room temperature. Ethanol was removed under reduced pressure. The crude product was taken in to aqueous 2N NaOH solution (100 mL) and extracted with 3:1 CH2Cl2/THF (4×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure yielding crude product. The crude product was purified by flash chromatography (neutral alumina, Brockmann activity II-III) eluting with 9:1 ethyl acetate/hexane to afford 1.43 g (96%) of 19 as a white solid (mixture of E/Z): LCMS (ESI): m/z 303.5 (M+H)+.

Workup

  1. temperatureto reflux for 5 h
  2. customEthanol was removed under reduced pressure
  3. extractionextracted with 3:1 CH2Cl2/THF (4×50 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customyielding crude product
  8. customThe crude product was purified by flash chromatography (neutral alumina, Brockmann activity II-III)
  9. washeluting with 9:1 ethyl acetate/hexane

Sources & evidence

ORD record
ord-8311d53e8ea040ee98f115ceec353342
Source dataset
uspto-grants-2009_01
Patent number
US07476679B2

Reaction notes

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