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

HRID 1992780Notes

Reaction equation

HRID 1992780 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].[CH3:49][N:50]([CH3:66])[CH2:51][C@H:52]([CH3:65])[C@:53]([C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([O:63][CH3:64])[CH:58]=1)([OH:56])[CH2:54][CH3:55].[C:67]([OH:76])(=[O:75])[CH:68]([CH:70]([C:72]([OH:74])=[O:73])[OH:71])[OH:69]>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][CH: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:72]([CH:70]([CH:68]([C:67]([OH:76])=[O:75])[OH:69])[OH:71])([OH:74])=[O:73].[CH3:66][N:50]([CH3:49])[CH2:51][C@H:52]([CH3:65])[C@@:53]([C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([O:63][CH3:64])[CH:58]=1)([OH:56])[CH2:54][CH3:55].[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].[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

10

Reactant 5

HCID 8752,3-Dihydroxybutanedioic AcidHCID 444305L-Tartaric acidHCID 9942979(alphaR)-alpha-[(1S)-2-(Dimethylamino)-1-methylethyl]-alpha-ethyl-3-methoxybenzenemethanolHCID 11522448Talabostat mesylateHCID 11708619(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol2×

Product 4

HCID 731702091-Dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrateHCID 86624367(2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrateYield 0.8%HCID 86624368(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrateYield 98.2%HCID 86624369(2S,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (+)-tartrate

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 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.

Workup

  1. temperatureheating system
  2. customdried in a drying cabinet at 50° C. for 12 h under reduced pressure to a final pressure of 20 mbar

Sources & evidence

ORD record
ord-3c5403c3f2734cf7b2b78ec4541e4269
Source dataset
uspto-grants-2010_01
Patent number
US07649114B2

Reaction notes

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