Lawesson's reagent → HCID 90025425, compound

HRID 920167Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C@@:8]2([CH3:20])[NH:16][C:15](=O)[C:11]3([CH2:14][CH2:13][CH2:12]3)[S:10](=[O:19])(=[O:18])[CH2:9]2)[CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:31])=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C@@:8]2([CH3:20])[NH:16][C:15](=[S:31])[C:11]3([CH2:14][CH2:13][CH2:12]3)[S:10](=[O:19])(=[O:18])[CH2:9]2)[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (R)-7-(5-bromo-2-fluoro-phenyl)-7-methyl-5,5-dioxo-5λ6-thia-8-aza-spiro[3.5]nonan-9-one (1.1 g, 2.92 mmol, Eq: 1.00) in dioxane (50 ml) was added Lawesson's reagent (1.18 g, 2.92 mmol, Eq: 1.00). The reaction mixture was stirred at 80° C. for 2 hours. More Lawesson's reagent (1.55 g, 3.84 mmol, Eq: 1.00) was added and stirring continued at 80° C. for 8 hours. The reaction mixture was poured into sat. NaHCO3 solution and extracted twice with ethyl acetate. The organic layers were washed with brine, dried over Na2SO4, filtered and evaporated to give light yellow oil. The residue was chromatographed on 20 g silica gel with 0-50% ethyl acetate in heptane to give (R)-7-(5-bromo-2-fluoro-phenyl)-7-methyl-5,5-dioxo-5λ6-thia-8-aza-spiro[3.5]nonan-9-thione (1.05 g, 2.68 mmol, 91.5% yield) as a light yellow foam. MS (ISP): m/z=392.0 [M+H]+ and 394.3 [M+2+H]+.

Workup

stirringstirring
waitcontinued at 80° C. for 8 hours
extractionextracted twice with ethyl acetate
washThe organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customto give light yellow oil
customThe residue was chromatographed on 20 g silica gel with 0-50% ethyl acetate in heptane

Sources & evidence

ORD record: ord-09d30acbf25b40d0a7077f24a8d60eb8
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273042B2

Reaction notes

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