L-Tartaric acid → 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester-L-(+)-tartrate salt

HRID 1269496Notes

Reaction equation

HRID 1269496 reaction equation
[C:1]([OH:10])(=[O:9])[C@@H:2]([C@H:4]([C:6]([OH:8])=[O:7])[OH:5])[OH:3].[CH2:11]([O:18][C:19](=[O:36])[C:20]([CH3:35])([O:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH:29]2[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]2)[CH:24]=1)[CH3:21])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O.CC(=O)CC>[C:6]([C@@H:4]([C@H:2]([C:1]([OH:10])=[O:9])[OH:3])[OH:5])([OH:8])=[O:7].[CH2:11]([O:18][C:19](=[O:36])[C:20]([CH3:21])([O:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH:29]2[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]2)[CH:24]=1)[CH3:35])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

4

Reactant 2

HCID 444305L-Tartaric acidHCID 688839562-Methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester

Product 1

HCID 1317263192-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester-L-(+)-tartrate saltYield 44%

Reagents, catalysts & solvents 1

HCID 19370624Water 2-butanoneSolvent2×

Procedure

To a solution of L-(+)-tartaric acid in refluxing 2.5% water/2-butanone (105 mL) was added 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester (Preparation 2, Method C; 9.11 g, 25.8 mmol) in 2.5% water/2-butanone (20 mL). The resulting solution was allowed to cool to ambient temperature with stirring. As the mixture cooled, a white solid precipitated out. The suspension was allowed to stir at ambient temperature for 64 h. The precipitate was collected on a Buchner funnel and rinsed with 2-butanone and dried under vacuum to yield 5.66 g (44%) of 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester-L-(+)-tartrate salt (87.5% ee). The white solid was slurried in 2.5% water/2-butanone (59.5 mL) and heated to reflux. Water was added slowly until the milky suspension became clear. The resulting solution was allowed to cool to ambient temperature with stirring. As the mixture cooled, a white solid precipitated out. The suspension was allowed to stir at ambient temperature for 64 h. The precipitate was collected on a Buchner funnel and rinsed with 2-butanone and dried under vacuum to yield 4.86 g (37% overall) of (S)-2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester-L-(+)-tartrate salt (98% ee; [α]D25=11.2° (c 0.86, CH3OH); HPLC analysis: chiralpak AD 1.5 mL/min, 5% isopropanol/hexanes w/0.5% diethylamine, retention time=6.65 min (R) and 8.08 min (S)).

Workup

  1. temperatureAs the mixture cooled
  2. customa white solid precipitated out
  3. stirringto stir at ambient temperature for 64 h
  4. customThe precipitate was collected on a Buchner funnel
  5. washrinsed with 2-butanone
  6. customdried under vacuum

Sources & evidence

ORD record
ord-ccc0b16742f74bcb961513ae1bd7ff25
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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