Water → 1-(3,4,5-Trimethoxybenzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

HRID 323240Notes

Reaction equation

HRID 323240 reaction equation
C([C@](C(O)=O)(O)[C@](C(=O)C1C=CC(OC)=CC=1)(O)C(O)=O)(=O)C1C=CC(OC)=CC=1.[C:31]1([C:37]2([CH2:42][CH2:43][OH:44])[CH2:41][CH2:40][NH:39][CH2:38]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.O.C(=O)([O-])[O-].[K+].[K+].[CH3:52][O:53][C:54]1[CH:55]=[C:56]([CH:60]=[C:61]([O:65][CH3:66])[C:62]=1[O:63][CH3:64])[C:57](Cl)=[O:58]>CC(C)=O>[CH3:66][O:65][C:61]1[CH:60]=[C:56]([CH:55]=[C:54]([O:53][CH3:52])[C:62]=1[O:63][CH3:64])[C:57]([N:39]1[CH2:40][CH2:41][C:37]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([CH2:42][CH2:43][OH:44])[CH2:38]1)=[O:58]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 70109704(-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

Product 1

HCID 184649591-(3,4,5-Trimethoxybenzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
0 °C

Procedure

Combine (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt (3.95 g, 6.48 mmol) and acetone (20 mL), water (6 mL), and potassium carbonate (2.70 g, 19.5 mmol). Cool to 0° C. in an ice bath. After 30 minutes, add dropwise a solution of 3,4,5-trimethoxybenzoyl chloride (1.71 9, 7.4 mmol) in acetone (20 mL). Warm to ambient temperature. After 18 hours, partition the reaction mixture between ethyl acetate and saturated aqueous sodium bicarbonate solution. Separate the organic layer and extract with brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give the title compound: Rf=0.23 (silica gel, ethyl acetate). 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 of 22.30 minutes.

Workup

  1. temperatureWarm to ambient temperature
  2. waitAfter 18 hours
  3. custompartition the reaction mixture between ethyl acetate and saturated aqueous sodium bicarbonate solution
  4. customSeparate the organic layer
  5. extractionextract with brine
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. customevaporate in vacuo

Sources & evidence

ORD record
ord-bae0734a1f9c4d1e958af6123fb021c8
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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