Trifluoroacetic acid → (R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-one

HRID 920163Notes

Reaction equation

HRID 920163 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C@@:8]2([CH3:32])[N:17](CC3C=CC(OC)=CC=3OC)[C:16](=[O:29])[C:11]3([CH2:15][CH:14]=[CH:13][CH2:12]3)[S:10](=[O:31])(=[O:30])[CH2:9]2)[CH:7]=1.FC(F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O.C([O-])([O-])=O.[Na+].[Na+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C@@:8]2([CH3:32])[NH:17][C:16](=[O:29])[C:11]3([CH2:12][CH:13]=[CH:14][CH2:15]3)[S:10](=[O:31])(=[O:30])[CH2:9]2)[CH:7]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 62406Trifluoromethanesulfonic acidHCID 90024531(R)-8-(5-bromo-2-fluoro-phenyl)-9-(2,4-dimethoxy-benzyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-one

Product 1

HCID 90025282(R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-oneYield 94.3%

Conditions

Temperature
23 °C

Procedure

A mixture of (R)-8-(5-bromo-2-fluoro-phenyl)-9-(2,4-dimethoxy-benzyl)-8-methyl-6,6-dioxo-6λ6-thia-9-aza-spiro[4.5]dec-2-en-10-one (450 mg, 836 μmol, Eq: 1.00) and trifluoroacetic acid (9.53 g, 6.44 ml, 83.6 mmol, Eq: 100) was stirred at 23° C. After 1 hour trifluoromethanesulfonic acid (251 mg, 148 μl, 1.67 mmol, Eq: 2.0) was added and the dark red solution was stirred 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 10 g silica gel with heptane/ethyl acetate 1:1 to give (R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6λ6-thia-9-aza-spiro[4.5]dec-2-en-10-one (340 mg, 788 μmol, 94.3% yield) as a white solid. MS (ISP): m/z=388.1 [M+H]+ and 390.2 [M+2+H]+.

Workup

  1. stirringthe dark red solution was stirred for 2 hours
  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 10 g silica gel with heptane/ethyl acetate 1:1

Sources & evidence

ORD record
ord-aba03d8fa3f54e928f72652f7c05e3c5
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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