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

HRID 1500452ノート

反応式

HRID 1500452 の反応式
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

参加物

5

反応物 2

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

生成物 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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-4f2c5b51259244328347b2384dbc2a3e
出典データセット
uspto-grants-2015_12
特許番号
US09206116B2

反応ノート

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