Citric Acid → HCID 66739033, compound

HRID 1021067Notes

Reaction equation

HRID 1021067 reaction equation
[C:1]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=[CH:5][C:4]([CH2:7][CH:8]2[NH:12][C:11](=[O:13])[C:10]([CH3:17])([C:14]([OH:16])=[O:15])[CH2:9]2)=[CH:3][CH:2]=1.C1(C)C=CC=CC=1.[C:31](Cl)(=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O.C(N(CC)CC)C>[C:1]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C:11](=[O:13])[C@:10]([CH3:17])([C:14]([OH:16])=[O:15])[CH2:9]2)=[CH:5][CH:6]=1.[C:1]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C:11](=[O:13])[C@@:10]([CH3:17])([C:14]([OH:16])=[O:15])[CH2:9]2)=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 1140TolueneHCID 62493Pivaloyl chlorideHCID 69042110HCID 69042110, compound

Product 2

HCID 66739033HCID 66739033, compoundHCID 66739161HCID 66739161, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

44 mg (3R/S, 5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid (R1=H; R10=OH; R11=Me) [66:34 mixture of C3-stereoisomers] are added to 10 ml toluene. 119 μl Triethylamine are added and the resulting mixture warmed to 60° C. 52 μl Pivaloyl chloride are added and the mixture is stirred for 4 h. The mixture is then cooled to room temperature. 250 mg Citric acid in water (5 ml) is added and the phases are separated. The organic phase is washed with water, dried (MgSO4) and concentrated in vacuo to give (3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid (R1=Piv; R10=OH; R11=Me) and (3S,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid (R1=Piv; R10=OH; R11=Me). According to HNMR analysis the ratio of C3 diastereoisomers is 65:35. Identity of major diastereomer not determined. 1H NMR (CDCl3) [Mixture of stereoisomers]: 1.19 (9H), 1.21 (3H), 1.73-1.91 (1H), 2.23 (1H), 2.50 (2H), 3.12-3.33 (1H), 4.45-4.60 (1H), 7.19 (1H), 7.27 (2H), 7.37 (2H), 7.46 (4H).

Workup

  1. temperatureThe mixture is then cooled to room temperature
  2. customthe phases are separated
  3. washThe organic phase is washed with water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3e02160ea0c24d818d2cca67e39602cd
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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