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

HRID 882511Notes

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(N(CC)CC)C.[C:27](Cl)(=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1>[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:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])[C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 60 °C

Procedure

(S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) (100 g, 398 mmol) and triethylamine (166 ml, 1.2 mol) are added to toluene (1 L) at room temperature. The mixture is heated to 60° C. Pivaloyl chloride (73.5 ml, 597 mmol) is added over 2 h. After a further 1 h, citric acid solution (237 g in 1 L) is added and the phases are separated. The water phase is washed with toluene (0.5 L). The organic portions are combined, washed with water (0.5 L) and then dried (MgSO4). The mixture is concentrated in vacuo. The residue is suspended in heptane (550 ml) and is heated to reflux. The mixture is then cooled to room temperature. After 1 h, the mixture is cooled to 0° C., and then filtered to give (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (1, R1=pivaloyl)

Workup

customthe phases are separated
washThe water phase is washed with toluene (0.5 L)
washwashed with water (0.5 L)
dry with materialdried (MgSO4)
concentrationThe mixture is concentrated in vacuo
temperatureis heated to reflux
temperatureThe mixture is then cooled to room temperature
waitAfter 1 h
temperaturethe mixture is cooled to 0° C.
filtrationfiltered

Sources & evidence

ORD record: ord-403da216f1ea4a5887695360a0ba859b
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993785B2

Reaction notes

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