2-Propanol, 2-methyl-, lithium salt (1:1) → (r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 588319ノート

反応式

HRID 588319 の反応式
C[C:2]([CH3:5])([O-])[CH3:3].[Li+].[C:7]([O:11][C:12]([N:14]1[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>O1CCCC1>[C:7]([O:11][C:12]([N:14]1[C@H:15]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[CH2:16]/[C:17](=[CH:12]\[N:14]([CH:15]([CH3:20])[CH3:16])[CH:2]([CH3:5])[CH3:3])/[C:18]1=[O:19])=[O:13])([CH3:10])([CH3:8])[CH3:9]

参加物

4

反応物 2

HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 46193436(S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

生成物 1

HCID 58160400(r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

A mixture of lithium tert-butoxide (2.8 eq, 2.8 mmol, 1 M solution in THF) and N,N,N′N′-tetramethylformamidinium chloride (18, R6=Me, R7=Me) (3 eq, 3 mmol) are stirred at 60° C. for 1 h. The mixture is then cooled to room temperature. The mixture is then diluted with tetrahydrofuran to a total volume of 5 ml. (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (8-a, R1=Boc) (1 eq, 1 mmol) is then added to the mixture. The mixture is then stirred at room temperature for 3 h. The volatiles are removed under reduced pressure. Ethyl acetate (20 ml) is added to the mixture. The phases are separated and the organic phase is washed with saturated sodium carbonate solution (2×20 ml) and brine (20 ml). The organic phase is dried (Na2SO4) and concentrated under reduced pressure to afford (R)-5-Biphenyl-4-ylmethyl-3-[1-dimethylaminometh-(E/Z)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7-a, R1=Boc, R6=Me, R7=Me) or a salt thereof. The solutions are analysed by TLC (50% ethyl acetate in hexane). RF 0.21 (salt of 7-a, R1=Boc, R6=Me, R7=Me); RF 0.27 (7-a, R1=Boc, R6=Me, R7=Me); RF 0.68 (8-a, R1=Boc).

後処理

  1. temperatureThe mixture is then cooled to room temperature
  2. stirringThe mixture is then stirred at room temperature for 3 h
  3. customThe volatiles are removed under reduced pressure
  4. additionEthyl acetate (20 ml) is added to the mixture
  5. customThe phases are separated
  6. washthe organic phase is washed with saturated sodium carbonate solution (2×20 ml) and brine (20 ml)
  7. dry with materialThe organic phase is dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-a8bad162e03b4b3dbe6e093aafcd71df
出典データセット
uspto-grants-2016_01
特許番号
US09227934B2

反応ノート

読み込み中…