Lawesson's reagent → (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1lambda6-thiomorpholin-3-thione

HRID 920165Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@@:8]2([CH3:19])[NH:13][C:12](=O)[C:11]([CH3:16])([CH3:15])[S:10](=[O:18])(=[O:17])[CH2:9]2)[CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:30])=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@@:8]2([CH3:19])[NH:13][C:12](=[S:30])[C:11]([CH3:16])([CH3:15])[S:10](=[O:18])(=[O:17])[CH2:9]2)[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1λ6-thiomorpholin-3-one (1.4 g, 3.84 mmol, Eq: 1.00) in dioxane (29.5 ml) was added Lawesson's reagent (3.10 g, 7.68 mmol, Eq: 2.00). The reaction mixture was stirred at 80° C. for 10 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 a light yellow oil. The residue was chromatographed on 20 g silica gel with ethyl acetate in heptane to give (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1λ6-thiomorpholin-3-thione (1.3 g, 3.42 mmol, 88.9% yield) as a light yellow foam. MS (ISP): m/z=380.0 [M+H]+ and 382.3 [M+2+H]+.

Workup

extractionextracted twice with ethyl acetate
washThe organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customto give a light yellow oil
customThe residue was chromatographed on 20 g silica gel with ethyl acetate in heptane

Sources & evidence

ORD record: ord-b3f28cc96ce04b269310e22afbc2bc26
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273042B2

Reaction notes

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