Hydrochloric Acid → (-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

HRID 323236Notes

Reaction equation

HRID 323236 reaction equation
[C:1]([C@:11]([C:28]([OH:30])=[O:29])([OH:27])[C@:12]([C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)([OH:16])[C:13]([OH:15])=[O:14])(=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.Cl.[C:32]1([C:38]2([CH2:43][CH2:44][OH:45])[CH2:42][CH2:41][NH:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O.CO.CO>[C:17]([C@:12]([C:13]([OH:15])=[O:14])([OH:16])[C@:11]([C:1](=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1)([OH:27])[C:28]([OH:30])=[O:29])(=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1.[C:32]1([C:38]2([CH2:43][CH2:44][OH:45])[CH2:42][CH2:41][NH:40][CH2:39]2)[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 184645642-(3-Phenylpyrrolidin-3-yl)ethanolHCID 66875417(R, R)-di-p-anisoyltartaric acid

Product 1

HCID 70109704(-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

Combine (R,R)-di-p-anisoyltartaric acid (1.10 g, 2.62 mmol) in water/methanol (13.6 mL/13.6 mL). Add 12 M hydrochloric acid solution (0.217 mL, 2.63 mmol). Add a hot solution of 3-phenyl-3-(2-hydroxyethyl)pyrrolidine (1.0 g, 5.23 mmol) in methanol (13.6 mL). Heat to reflux. After 30 minutes, slowly cool to ambient temperature to give a solid. Collect the solid by filtration and recrystallize the solid twice from methanol/water, once from methanol/2-butanone, and once from ethanol to give (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid. After conversion of a sample to the 3,4,5-trimethoxybenzamide using sodium carbonate and 3,4,5-trimethoxybenzoyl chloride in acetone/water, analysis on HPLC using a CHIRALPAK AD (10 μm×4.6 cm×250 cm) column eluting with pentane/ethanol/methanol/triethylamine (80/15/5/0.1) with a flow rate of 1.5 mL/minute indicates an enantiomeric excess of 98%, (98% ee), retention time 22.30 minutes for the 3,4,5-trimethoxybenzamide of the isomer prepared from the (−)-isomer of (R,R)-di-p-anisoyltartaric acid salt.

Workup

  1. temperatureHeat to reflux
  2. customto give a solid
  3. customCollect the solid
  4. filtrationby filtration
  5. customrecrystallize the solid twice from methanol/water

Sources & evidence

ORD record
ord-dfa591f770c24733aecf4bea42eecacd
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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