HCID 67969538, compound → (S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

HRID 2273470Notes

Reaction equation

HRID 2273470 reaction equation
[C:1]([O:5][C:6](=[O:33])[NH:7][C@@H:8]([CH2:22][CH:23]1C(=O)OC(C)(C)O[C:24]1=[O:32])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:7]1[C:24](=[O:32])[CH2:23][CH2:22][C@H:8]1[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:14][CH:15]=1)=[O:33])([CH3:3])([CH3:4])[CH3:2]

Participants

3

Reactant 1

HCID 67969538HCID 67969538, compound

Product 1

HCID 46193436(S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of [(S)-2-Biphenyl-4-yl-1-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-ylmethyl)ethyl]-carbamic acid t-butyl ester (143 g, 320 mmol) in anhydrous toluene (1 L) was heated to reflux under nitrogen overnight. The solvent was removed under reduced pressure to give (S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester, which was directly used without further purification and added to a solution of 3N HCl in EtOAc (1.2 L). The resulting mixture was stirred for 3 hours at room temperature. The solvent was removed in vacuo. The residue was re-crystallized in EtOAc (300 mL) to yield a first batch of the deprotected compound (56 g). The mother liquid was subject to chromatography column (eluted by EtOAc and hexanes from 1:1 to 100% EtOAc) to yield a second batch of the deprotected compound (8 g). To a suspension of the deprotected compound (64 g, 250 mmol) in anhydrous THF (500 mL) was added dropwise BuLi (100 mL, 2.5 M in hexanes) at −78° C. After stirring for 0.5 hour, pivaloyl chloride (34 g, 0.28 mol) was added dropwise. The mixture was stirred for 1 hour at −78° C. The reaction was then quenched with saturated aqueous NH4Cl, and the mixture extracted with EtOAc. The extract was dried over MgSO4 and concentrated to yield (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (85 g) as white solid.

Workup

  1. temperatureto reflux under nitrogen overnight
  2. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-526057f1697049ea9122de7c0437c6c3
Source dataset
uspto-grants-2015_09
Patent number
US09120747B2

Reaction notes

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