Lawesson's reagent → (6S)-1-(2-chloro-3-(trifluoromethyl)benzyl)-6-ethyl-3-thioxopiperazin-2-one

HRID 576699Notes

Reaction equation

COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[Cl:23][C:24]1[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:38]=[CH:37][C:25]=1[CH2:26][N:27]1[C@@H:32]([CH2:33][CH3:34])[CH2:31][NH:30][C:29](=O)[C:28]1=[O:36]>C1COCC1>[Cl:23][C:24]1[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:38]=[CH:37][C:25]=1[CH2:26][N:27]1[C@@H:32]([CH2:33][CH3:34])[CH2:31][NH:30][C:29](=[S:10])[C:28]1=[O:36]

Participants

Conditions

Temperature: 55 °C

Procedure

To a heterogeneous mixture of Lawesson's reagent (346 mg, 0.83 mmol) in THF (16 mL) was added (6S)-1-(2-chloro-3-(trifluoromethyl)benzyl)-6-ethylpiperazine-2,3-dione (555 mg, 1.7 mmol) at once. The mixture was heated at 55° C. for 20 minutes and then concentrated to remove the solvent. Purification by chromatography (SiO2; hexanes—100% EtOAc) afforded the desired product as a yellow oil (528 mg, 91%). MS (ESI): mass calcd. for C14H14ClF3N2OS, 350.1; m/z found, 335.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.69 (dd, J=15.9, 7.8 Hz, 2H), 7.38 (t, J=7.8 Hz, 1H), 5.24 (d, J=15.3 Hz, 1H), 4.50 (d, J=15.3 Hz, 1H), 3.67 (dd, J=13.7, 3.9 Hz, 1H), 3.45 (dd, J=12.8, 5.4 Hz, 2H), 1.91-1.75 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

Workup

concentrationconcentrated
customto remove the solvent
customPurification by chromatography (SiO2; hexanes—100% EtOAc)

Sources & evidence

ORD record: ord-cf38e5d5fa62426e88fc3ef5fa1da2a9
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040534B2

Reaction notes

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