2-(3-(3,4-Dichlorophenyl)pyrrolidin-3-yl)ethanol → (S)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

HRID 1601422Notes

Reaction equation

HRID 1601422 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:14][CH2:15][OH:16])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[C:17]([C@:27]([C:44]([OH:46])=[O:45])([OH:43])[C@:28]([C:33](=[O:42])[C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)([OH:32])[C:29]([OH:31])=[O:30])(=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1>CC(=O)CC>[C:33]([C@:28]([C:29]([OH:31])=[O:30])([OH:32])[C@:27]([C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)([OH:43])[C:44]([OH:46])=[O:45])(=[O:42])[C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1.[Cl:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH2:14][CH2:15][OH:16])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 184644272-(3-(3,4-Dichlorophenyl)pyrrolidin-3-yl)ethanolHCID 66875417(R, R)-di-p-anisoyltartaric acid

Product 1

HCID 131720896(S)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

Combine 3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine (1.0 g, 38.5 mmol) and butanone. Add a solution of (R,R)-di-p-anisoyltartaric acid (106 g, 38.0 mmol) in butanone (80 mL). Heat to reflux. After 15 minutes, cool to ambient temperature and then cool further in an salt-ice bath. Filter the solid that forms and rinse with butanone. Recrystallize the solid from water/methanol to give (S)-(-)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt: mp; 201-204° C. (dec). [α]2D0 =-18.9°(c=0.60, dimethylsulfoxide). X-ray diffraction analysis of a single crystal confirms the (S)-configuration. Analysis on HPLC, on an analytical sample of the free amine obtained by extraction, using a CHIRALPAK AD 25 cm×0.46 cm column eluting with pentane/methanol/triethylamine (80/10/0.1) with a flow rate of 1.0 mL/minute indicates an enantiomeric excess of 96%, (96% ee), retention time of the (S)-isomer 11.2 minutes, retention time of the (R)-isomer 14.5 minutes.

Workup

  1. temperatureHeat to reflux
  2. temperaturecool further in an salt-ice bath
  3. filtrationFilter the solid that forms
  4. washrinse with butanone
  5. customRecrystallize the solid from water/methanol

Sources & evidence

ORD record
ord-58a2c167ace64a6bba4fac2f06e84d5c
Source dataset
uspto-grants-1999_11
Patent number
US05977139

Reaction notes

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