Pivaloyl chloride → (S)-5-[(biphenyl-4-yl)methyl]-1-(2,2-dimethylpropionyl)pyrrolidin-2-one

HRID 1021026Notes

Reaction equation

[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.C([Li])CCC.[C:25](Cl)(=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[C:1]1([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:5][CH:6]=1

Participants

Conditions

Temperature: -78 °C

Procedure

20 g of (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) of example 3 were dissolved in 200 ml tetrahydrofuran. The mixture was cooled to about −78° C. and 55 ml n-butyllithium (1.6 M) were added. After about 0.5 hours, 11.8 ml of pivaloyl chloride were added. After 1 hour, the mixture was quenched with 210 ml ammonium chloride solution and extracted with 70 ml ethyl acetate. The mixture was concentrated to dryness to obtain 26.7 g of (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (1, R1=pivaloyl). 1H-NMR (CDCl3): 1.40 (9H, s, C(CH3)3); 1.91 (1H, m, 4-CHH); 2.03 (1H, m, 4-CHH); 2.47 (1H, m, 3-CHH); 2.55 (1H, m, 3-CHH); 2.74 (1H, dd, 1-CHH); 3.18 (1H, dd, 1-CHH); 4.67 (1H, m, 5-CH); 7.34 (2H, m, aromatic); 7.36 (1H, m, aromatic); 7.46 (2H, m, aromatic); 7.58 (4H, m, aromatic). m/z: 336 (MH+, 100%).

Workup

waitAfter 1 hour
customthe mixture was quenched with 210 ml ammonium chloride solution
extractionextracted with 70 ml ethyl acetate
concentrationThe mixture was concentrated to dryness

Sources & evidence

ORD record: ord-945ddd56e0954c8e93a26cd7c7347a1e
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716495B2

Reaction notes

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