Acetyl chloride → 1-(3-(Benzyloxy)phenyl)-3-(dimethylamino)-2-methylpropan-1-one

HRID 534697Notes

Reaction equation

HRID 534697 reaction equation
CC[C@H]([C@H](CN(C)C)C)C1C=CC=C(O)C=1.[CH2:17]([O:24][C:25]1[CH:26]=[C:27]([C:31](=[O:34])[CH2:32][CH3:33])[CH:28]=[CH:29][CH:30]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[CH3:36][N+:37](=[CH2:39])[CH3:38].C(Cl)(=O)C>C(#N)C>[CH2:17]([O:24][C:25]1[CH:26]=[C:27]([C:31](=[O:34])[CH:32]([CH3:33])[CH2:39][N:37]([CH3:38])[CH3:36])[CH:28]=[CH:29][CH:30]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 9838022TapentadolHCID 11051579Dimethylmethylenammonium chlorideHCID 189555971-[3-(Benzyloxy)phenyl]propan-1-one

Product 1

HCID 250682011-(3-(Benzyloxy)phenyl)-3-(dimethylamino)-2-methylpropan-1-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

WO2008/012046 describes another method for the preparation of tapentadol, wherein 1-(3-(benzyloxy)phenyl)propan-1-one is reacted with N-Methyl-N-methylene-methaneaminium chloride in presence of acetyl chloride and solvent acetonitrile to obtain compound 1-(3-(benzyloxy)phenyl)-3-(dimethylamino)-2-methylpropan-1-one. The compound is resolved with L-(−)-dibenzoyltartaric acid to get (S)-1-(3-(benzyloxy)phenyl)-3-(dimethylamino)-2-methylpropan-1-one. The isolated compound is then reacted with ethyl magnesium bromide undergoing Grignard reaction to isolate (2S,3R)-3-(3-(benzyloxy)phenyl)-1-(dimethylamino)-2-methylpentan-3-ol, which on reaction with trifluoroacetic anhydride in acetic acid results in acetylated compound. The acetylated compound on hydrogenolysis results in the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I.

Sources & evidence

ORD record
ord-8c2a96ea38f94db39abdab64bf54f9a6
Source dataset
uspto-grants-2014_10
Patent number
US08853456B2

Reaction notes

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