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 751 of ethanol. Then, 10.55 kg (41.97 mol) of a racemic mixture of the enantiomeric pair (2R,3R)/(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol in 3.5 l of ethanol were introduced. The racemic mixture was enriched in respect of the enantiomer with the (2S,3S) configuration by addition of 1.06 kg (4.21 mol) of the enantiomerically pure compound (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. under reduced pressure for 12 h. After 24 h drying in a drying cabinet at 40° C. and a final pressure of 20 mbar, 8.34 kg (20.77 mol, 45% of theoretical) of (2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate were isolated as colourless crystals which were used as dried or moist with ethanol for release of the base. The other enantiomer (2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol could be isolated from the centrifugation mother liquor.

Provenance & Evidence