Trifluoroacetic acid → (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1lambda6-thiomorpholin-3-one

HRID 920162Notes

Reaction equation

HRID 920162 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@@:8]2([CH3:17])[NH:13][C:12](=O)[CH2:11][S:10](=[O:16])(=[O:15])[CH2:9]2)[CH:7]=1.F[C:20](F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O.[C:34]([O-:37])([O-])=O.[Na+].[Na+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@@:8]2([CH3:17])[NH:13][C:34](=[O:37])[C:11]([CH3:20])([CH3:12])[S:10](=[O:16])(=[O:15])[CH2:9]2)[CH:7]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 62406Trifluoromethanesulfonic acidHCID 90067097(R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1lambda6-thiomorpholin-3-one

Product 1

HCID 90016634(R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1lambda6-thiomorpholin-3-oneYield 94.2%

Conditions

Temperature
23 °C

Procedure

A mixture of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1λ6-thio morpholin-3-one (2.1 g, 4.08 mmol, Eq: 1.00) and trifluoroacetic acid (46.5 g, 31.5 ml, 408 mmol, Eq: 100) was stirred at 23° C. After 1 hour trifluoromethanesulfonic acid (1.23 g, 725 μl, 8.16 mmol, Eq: 2.0) was added and stirring continued for 2 hours. Poured into 1 M Na2CO3-sol. and extracted twice with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was chromatographed on 70 g silica gel with heptane/ethyl acetate 1:1 to give (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1λ6-thio morpholin-3-one (1.4 g, 3.84 mmol, 94.2% yield) as an off-white solid. MS (ISP): m/z=364.0 [M+H]+ and 366.3 [M+2+H]+.

Workup

  1. stirringstirring
  2. extractionand extracted twice with ethyl acetate
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was chromatographed on 70 g silica gel with heptane/ethyl acetate 1:1

Sources & evidence

ORD record
ord-853cea52702545c4bb84fa9adf753d21
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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