Brucine → (S)-1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid

HRID 2068250Notes

Reaction equation

HRID 2068250 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][C:11]([CH2:18][C:19]([CH3:21])=[CH2:20])([C:15]([OH:17])=[O:16])[CH2:10]1.COC1C=C2[C@@]34[C@@H]5C[C@H]6C(CN5CC3)=CCO[C@H]3CC(=O)N([C@H]4[C@@H]63)C2=CC=1OC>CC(O)C>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][C@:11]([CH2:18][C:19]([CH3:21])=[CH2:20])([C:15]([OH:17])=[O:16])[CH2:10]1

Participants

4

Reactant 2

HCID 442021BrucineHCID 670924761-(2,6-Dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid

Product 1

HCID 58218841(S)-1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid (prepared from step b, 9 g, 31.36 mmol) and brucine (12.37 g, 31.35 mmol) was added iPrOH (75 mL) and heated with stirring at 75° C. until it became a clear solution, which was then allowed to cool to room temperature slowly. The resulting white solid was filtered and discarded. The filtrate was then diluted with Et2O (100 mL) and washed with 2 N HCl (2×100 mL), dried (Na2SO4) and concentrated under reduced pressure to obtain (S)-1-(2,6-dimethyl-phenyl)-3-(2-methyl-allyl)-5-oxo-pyrrolidine-3-carboxylic acid (550 mg, enantiomeric ratio: 9:1, with the enantiomeric ratio determined using a RegisWhelk® chiral analytical column and 10% EtOH in hexanes isocratic solvent system, flow rate: 1 mL/min, 30 min run). Further recrystallization of the above carboxylic acid derivative from hot toluene/dioxane (9:1, 14 mL) enriched the enantiomeric ratio to 99.2:0.8 and afforded 430 mg of (S)-1-(2,6-dimethylphenyl)-3-(2-methylallyl)-5-oxo-pyrrolidine-3-carboxylic acid.

Workup

  1. temperatureheated
  2. temperatureto cool to room temperature slowly
  3. filtrationThe resulting white solid was filtered
  4. additionThe filtrate was then diluted with Et2O (100 mL)
  5. washwashed with 2 N HCl (2×100 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a7061ea8f37d4b178edadd00c9df483c
Source dataset
uspto-grants-2012_10
Patent number
US08293925B2

Reaction notes

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