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

HRID 588321Notes

Reaction equation

HRID 588321 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.[Li+].C(OC(O[C:45]([CH3:48])([CH3:47])C)N(C)C)(C)(C)C.[CH3:49][NH:50]C.O1[CH2:56][CH2:55][CH2:54]C1>>[C:1]([O:5][C:6]([N:8]1[C@H:9]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:19][CH:20]=2)[CH2:10]/[C:11](=[CH:49]\[N:50]([CH:45]([CH3:47])[CH3:48])[CH:55]([CH3:56])[CH3:54])/[C:12]1=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 5477121,1-bis(1,1-dimethylethoxy)-N,N,N-trimethylamineHCID 23688915Lithium hexafluorophosphateHCID 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

Procedure

351 mg (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (8-a, R1=Boc) (1 eq, 1 mmol) and lithium hexafluorophosphate (1 eq) is added to tetrahydrofuran (10 ml). N,N-Dimethylformamide di-tert-butyl acetal (15, R6=Me, R7=Me, R8=tBu) (3 eq) and dimethylamine (0.5 eq) are added to the mixture. The mixture is stirred at room temperature for 3 h. The volatiles are removed under reduced pressure. Ethyl acetate (20 ml) is then added. The mixture is washed with saturated sodium carbonate solution (2×20 ml) and then with brine (20 ml). The organic layer 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. customThe volatiles are removed under reduced pressure
  2. additionEthyl acetate (20 ml) is then added
  3. washThe mixture is washed with saturated sodium carbonate solution (2×20 ml)
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a80e308563904122b5133ee603775c2a
Source dataset
uspto-grants-2016_01
Patent number
US09227934B2

Reaction notes

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