Water → N-alpha-phenyl-ethyl-3,4-dimethoxy-amphetamine

HRID 1376870Notes

Reaction equation

HRID 1376870 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[CH2:6][C@H:7]([CH3:9])[NH2:8].CO[C:17]1[CH:18]=[C:19]([CH:24]=[CH:25][C:26]=1OC)[CH2:20][C@@H:21](C)N.O>C1C=CC=CC=1>[C:19]1([CH:20]([NH:8][CH:7]([CH2:6][C:5]2[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH3:9])[CH3:21])[CH:24]=[CH:25][CH:26]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 962WaterHCID 11095534(2S)-1-(3,4-Dimethoxyphenyl)propan-2-amineHCID 117694083,4-Dma, (R)-

Product 1

HCID 22918570N-alpha-phenyl-ethyl-3,4-dimethoxy-amphetamine

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Said synthesis was developed by D. E. Nichols et al. ("J. Med. Chem.", 1973, 16, 480-48 and U.S. Pat. No. 4,000,197, of 12.28.1976) and was applied to the chiral synthesis of several methoxylated amphetamines, including (S)-3,4-dimethoxy-amphetamine, which is an enantiomer of (3). In U.S. Pat. No. 4,000,197, the synthesis of the iminic intermediate is carried out in benzene under refluxing conditions during 24 hours with formed water being simultaneously azeotroped off; the hydrogenation is carried out with Raney-Nickel as the catalyst, in absolute ethanol under medium-pressure hydrogen (3 atm of H2). The N-α-phenyl-ethyl-3,4-dimethoxy-amphetamine (15) intermediate is isolated as hydrochloride salt, by crystallization in aqueous acetone or acetone/isopropanol blend, in moderate yield (relatively to dimethoxy-phenyl-acetone), of 48%.

Workup

  1. customSaid synthesis
  2. custom4,000,197, the synthesis of the iminic intermediate
  3. customsimultaneously azeotroped off

Sources & evidence

ORD record
ord-c4c02e9e2f2443b689ae59a997b92cbf
Source dataset
uspto-grants-1997_09
Patent number
US05663360

Reaction notes

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