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

HRID 1992778Notes

Reaction equation

HRID 1992778 reaction equation
B(O)(O)[C@H]1N(C([C@@H](N)C(C)C)=O)CCC1.CS(O)(=O)=O.[C@H:21]([OH:30])([C:27]([OH:29])=[O:28])[C@@H:22]([OH:26])[C:23]([OH:25])=[O:24].[CH3:31][N:32]([CH3:48])[CH2:33][C@H:34]([CH3:47])[C@@:35]([C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([O:45][CH3:46])[CH:40]=1)([OH:38])[CH2:36][CH3:37].C(O)(=O)C(C(C(O)=O)O)O>C(O)C>[C:23]([CH:22]([CH:21]([C:27]([OH:29])=[O:28])[OH:30])[OH:26])([OH:25])=[O:24].[CH3:48][N:32]([CH3:31])[CH2:33][C@H:34]([CH3:47])[C@@:35]([C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([O:45][CH3:46])[CH:40]=1)([OH:38])[CH2:36][CH3:37]

Participants

6

Reactant 4

HCID 8752,3-Dihydroxybutanedioic AcidHCID 444305L-Tartaric acidHCID 11522448Talabostat mesylateHCID 11708619(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol2×

Product 1

HCID 86624368(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrateYield 45%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

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.

Workup

  1. temperatureheating system
  2. customdried in a drying cabinet at 50° C. under reduced pressure for 12 h
  3. customAfter 24 h drying in a drying cabinet at 40° C.

Sources & evidence

ORD record
ord-5d97c83bbf0f46b7aabde95beeb05336
Source dataset
uspto-grants-2010_01
Patent number
US07649114B2

Reaction notes

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