2,3-Dihydroxybutanedioic Acid → (2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate

Participants

Reaction Steps

A 100 l double wall jacketed reaction vessel with electric impeller stirrer, Pt100 temperature sensor and oil-based cooling and heating system was charged with 6.93 kg (46.17 mol) of (+)-(2R,3R)-tartaric acid in 75 l of ethanol. Then a mixture of 10.55 kg (41.97 mol) of the enantiomeric pair (2R,3R)/(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (70%) and the enantiomeric pair (2R,3S)/(2S,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (30%) in 3.5 l of ethanol was enriched in respect of the enantiomer with the (2S,3S) configuration by the addition of 1.06 kg (4.21 mol) of the enantiomerically pure (2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol. This mixture was added to the prepared tartaric acid at 10° C. and stirred at a stirrer speed of 150 rpm for 20 hours. The crystals were centrifuged off and dried in a drying cabinet at 50° C. for 12 h under reduced pressure to a final pressure of 20 mbar. 5.93 kg (32% of theoretical) of colourless crystals of 1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate with a composition of the stereoisomers of 98.2% (2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate, 0.8% (2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate and 1% of the enantiomeric pair (2R,3S)/(2S,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate were obtained.

Provenance & Evidence