Trifluoroacetic acid → HCID 86584846, compound

HRID 1006808Notes

Reaction equation

HRID 1006808 reaction equation
[C:1](=[O:4])([O-])[O-].[K+].[K+].N([CH2:10][C@@H]1C[C@@H](SC(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)CN1S(C1C=CC2C(=CC=CC=2)C=1)(=O)=O)=[N+]=[N-].C(CC(=O)C)(=O)C.[CH3:56][C:57]1[N:61]([CH2:62][C@@H:63]2[CH2:67][C@@H:66]([S:68]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:65][N:64]2[S:88]([C:91]2[CH:100]=[CH:99][C:98]3[C:93](=[CH:94][CH:95]=[CH:96][CH:97]=3)[CH:92]=2)(=[O:90])=[O:89])[N:60]=[N:59][C:58]=1C(=O)C.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C.C([O-])(O)=O.[Na+]>CS(C)=O.O.C(#N)C>[SH:68][C@H:66]1[CH2:65][N:64]([S:88]([C:91]2[CH:100]=[CH:99][C:98]3[C:93](=[CH:94][CH:95]=[CH:96][CH:97]=3)[CH:92]=2)(=[O:89])=[O:90])[C@H:63]([CH2:62][N:61]2[C:57]([CH3:56])=[C:58]([C:1](=[O:4])[CH3:10])[N:59]=[N:60]2)[CH2:67]1

Participants

11

Reactant 7

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 31261AcetylacetoneHCID 516892Sodium BicarbonateHCID 69434650HCID 69434650, compoundHCID 86584838HCID 86584838, compound

Product 1

HCID 86584846HCID 86584846, compoundYield 73.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a suspension of 281 mg (2.0 mmol, 4 eq.) potassium carbonate in 2 ml DMSO were added 300 mg (0.51 mmol) (2S,4R)-2-azidomethyl-1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine and 72 μl (0.7 mmol, 1.38 eq) acetyl acetone. The reaction mixture was stirred at 40° C. for 3 d, diluted with water and extracted with Et2O, the layers were separated and the inorganic one was extracted with EtOAc, the combined organic layers were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica gel with EtOAc/hexane 1:1 yielding 249 mg (73%) (2S,4R)-1-{5-methyl-1-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidin-2-ylmethyl]-1H-[1,2,3]triazol-4-yl}-ethanone as white foam, MS: 673 (MH+). 150 mg (0.2 mmol) (2S,4R)-1-{5-methyl-1-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidin-2-ylmethyl]-1H-[1,2,3]triazol-4-yl}-ethanone were dissolved in 6.5 ml acetonitrile and 3 ml TFA and were treated with 0.5 ml triethylsilane at 40° C. for 4 h. The reaction mixture was added to a aqueous saturated NaHCO3 solution carefully, extracted, and the organic layer was washed with water and brine, dried over Na2SO4 and evaporated. Purification by column chromatography on silica gel with EtOAc/hexane 1:1 gave 63 mg (66%) (2S,4R)-1-[1-[4-mercapto-1-(naphthalene-2-sulfonyl)-pyrrolidin-2-ylmethyl]-5-methyl-1H-[1,2,3]triazol-4-yl]-ethanone as white solid, mp 145° C., MS: 431 (MH+).

Workup

  1. extractionextracted with Et2O
  2. customthe layers were separated
  3. extractionthe inorganic one was extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica gel with EtOAc/hexane 1:1 yielding 249 mg (73%) (2S,4R)-1-{5-methyl-1-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidin-2-ylmethyl]-1H-[1,2,3]triazol-4-yl}-ethanone as white foam, MS
  8. extractionextracted
  9. washthe organic layer was washed with water and brine
  10. dry with materialdried over Na2SO4
  11. customevaporated
  12. customPurification by column chromatography on silica gel with EtOAc/hexane 1:1

Sources & evidence

ORD record
ord-4de59e53ea714267ae949ef7ed90002e
Source dataset
uspto-grants-2004_09
Patent number
US06790860B2

Reaction notes

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