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

HRID 1477443Notes

Reaction equation

HRID 1477443 reaction equation
C[C:2]([CH3:5])([O-])[CH3:3].[K+].[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].[Cl-].[Li+]>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]

Participants

5

Reactant 3

HCID 433294Lithium ChlorideHCID 23665647Potassium tert-butoxideHCID 46193436(S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of potassium 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) and lithium chloride (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 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).

Workup

  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 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

Sources & evidence

ORD record
ord-2c79352280b24bd38844b2205ecce1b6
Source dataset
uspto-grants-2016_08
Patent number
US09403766B2

Reaction notes

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