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

HRID 2174841Notes

Reaction equation

HRID 2174841 reaction equation
CC(C)([O-])C.[K+].F[P-](F)(F)(F)(F)F.[CH:14]([N+:17]([CH:25]([CH3:27])[CH3:26])=[CH:18]N1CCCCC1)([CH3:16])[CH3:15].[C:28]([O:32][C:33]([N:35]1[C:39](=[O:40])[CH2:38][CH2:37][C@H:36]1[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[CH:44][CH:43]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>C1COCC1.C(OC(C)C)(=O)C>[C:28]([O:32][C:33]([N:35]1[C@H:36]([CH2:41][C:42]2[CH:43]=[CH:44][C:45]([C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[CH:46][CH:47]=2)[CH2:37]/[C:38](=[CH:18]\[N:17]([CH:14]([CH3:15])[CH3:16])[CH:25]([CH3:26])[CH3:27])/[C:39]1=[O:40])=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 46193436(S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl esterHCID 178457509HCID 178457509, compound

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 2

HCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 1 M solution of potassium tert-butoxide in THF (11.7 ml) is added to diisopropyl(piperidin-1-ylmethylidene)ammonium hexafluorophosphate (5 g, prepared according to Example 12). The resulting mixture is then stirred for 1 h at 50° C. (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (8-a, R1=Boc) (1 g) is then added to the reaction and the resulting mixture is stirred for 1 h at room temperature. The mixture is diluted with isopropyl acetate and filtered through silica. The residue is concentrated in vacuo then purified by column chromatography (ethyl acetate) to give (R)-5-biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(E)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7-a, R1=Boc, R6=iPr, R7=iPr). Rf 0.55 (ethyl acetate). 1H NMR (DMSO-d6), 7.65-7.62 (2H), 7.61-7.58 (2H), 7.47-7.42 (2H), 7.37-7.31 (1H), 7.29-7.25 (2H), 7.01 (1H), 4.28-4.20 (1H), 3.84-3.70 (2H), 3.07-3.01 (1H), 2.82-2.73 (1H), 2.71-2.63 (1H) 2.49-2.44 (1H), 1.49 (9H), 1.13-1.08 (12H).

Workup

  1. additionis then added to the reaction
  2. filtrationfiltered through silica
  3. concentrationThe residue is concentrated in vacuo
  4. customthen purified by column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-8d117a24b0c741f88393b384779267be
Source dataset
uspto-grants-2015_06
Patent number
US09061973B2

Reaction notes

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