Sodium Hydroxide → (3S,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid

HRID 882550Notes

Reaction equation

HRID 882550 reaction equation
C([O:3][C:4]([C@:6]1([CH3:31])[CH2:10][C@@H:9]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[N:8](C(=O)C(C)(C)C)[C:7]1=[O:30])=[O:5])C.[OH-].[Na+]>C(#N)C>[C:15]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:14]=[CH:13][C:12]([CH2:11][C@H:9]2[NH:8][C:7](=[O:30])[C@:6]([CH3:31])([C:4]([OH:5])=[O:3])[CH2:10]2)=[CH:17][CH:16]=1.[C:15]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:14]=[CH:13][C:12]([CH2:11][C@H:9]2[NH:8][C:7](=[O:30])[C@@:6]([CH3:31])([C:4]([OH:5])=[O:3])[CH2:10]2)=[CH:17][CH:16]=1

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 66739130(3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)3-methyl-2-oxo-pyrrolidine-3-carboxylic acid ethyl ester

Product 2

HCID 66738939(3S,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acidHCID 66739144(3R,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

252 mg (3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid ethyl ester (R1=Piv; R10=OEt; R11=Me) [62:38 mixture of C3-isomers] is added to 1 ml acetonitrile at 0° C. 0.3 ml 3 M Sodium hydroxide solution is added and the mixture stirred at room temperature for 20 h. Two further 50 μl portions of 3 M sodium hydroxide are added. Stirring is continued for another 2 h. The mixture is concentrated in vacuo. 2.5 ml of water is added to the residue and it is then extracted twice with 1 ml toluene. 5 ml Ethyl acetate is added to the aqueous phase, which is then cooled to 0° C. 500 μl 2 M Hydrochloric acid is added and the phases are separated. The aqueous phase is then extracted with ethyl acetate. The combined organic phases are combined, dried (MgSO4) and concentrated in vacuo to afford (3R,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid (R1=H; R10=OH; R11=Me) and (3S,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid (R1=H; R10=OH; R11=Me). According to HNMR analysis there is a 66:34 mixture of C3-stereoisomers. Identity of major isomer not determined. 1H NMR (DMSO) [mixture of stereoisomers]: 1.21 (3H), 1.59, 1.84, 2.20, 2.29 (total 2H), 2.66 (1H), 2.93 (1H), 3.81 (1H), 7.31 (3H), 7.44 (2H), 7.60 (4H), 8.10, 8.15 (total 1H), 12.58 (1H).

Workup

  1. stirringStirring
  2. waitis continued for another 2 h
  3. concentrationThe mixture is concentrated in vacuo
  4. addition2.5 ml of water is added to the residue and it
  5. extractionis then extracted twice with 1 ml toluene
  6. addition5 ml Ethyl acetate is added to the aqueous phase, which
  7. temperatureis then cooled to 0° C
  8. addition500 μl 2 M Hydrochloric acid is added
  9. customthe phases are separated
  10. extractionThe aqueous phase is then extracted with ethyl acetate
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ab5d1efabf4146238c28a68db77221be
Source dataset
uspto-grants-2015_03
Patent number
US08993785B2

Reaction notes

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