Trifluoromethanesulfonic anhydride → HCID 11767974, compound

HRID 2306212Notes

Reaction equation

HRID 2306212 reaction equation
[C:1]([O:5][C:6](=[O:68])[N:7]([C@H:34]1[CH2:38][CH2:37][N:36]([C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([O:49][Si:50]([C:63]([CH3:66])([CH3:65])[CH3:64])([C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=4)[C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[CH:47]=3)[CH:42]=[CH:41][CH:40]=2)[C:35]1=[O:67])[CH2:8][CH2:9][C:10]1[N:11]=[CH:12][N:13](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].[C:69]([C:71]1[CH:78]=[CH:77][C:74]([CH2:75]O)=[CH:73][C:72]=1[F:79])#[N:70].C(N(CC)C(C)C)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl>[C:1]([O:5][C:6](=[O:68])[N:7]([C@H:34]1[CH2:38][CH2:37][N:36]([C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([O:49][Si:50]([C:63]([CH3:66])([CH3:65])[CH3:64])([C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)[C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=4)[CH:47]=3)[CH:42]=[CH:41][CH:40]=2)[C:35]1=[O:67])[CH2:8][CH2:9][C:10]1[N:11]([CH2:75][C:74]2[CH:77]=[CH:78][C:71]([C:69]#[N:70])=[C:72]([F:79])[CH:73]=2)[CH:12]=[N:13][CH:14]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 10887513HCID 10887513, compoundHCID 118296312-Fluoro-4-(hydroxymethyl)benzonitrile

Product 1

HCID 11767974HCID 11767974, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-{1-[7-(tert-butyldiphenylsilyloxy)naphthalen-1-yl]-2-oxo-pyrrolidin-3-yl}-{2-[1-(triphenylmethyl)-1H-imidazol-4-yl]ethyl}carbamic acid tert-butyl ester, as described above in Step G, (720 mg, 0.785 mmol) and 4-cyano-3-fluorobenzyl alcohol, as described above in Step H, (142 mg, 0.940 mmol) in dry CH2Cl2 (7 mL) were added N,N-diisopropylethylamine (0.342 mL, 1.96 mmol), followed by trifluoromethanesulfonic anhydride (0.158 mL, 0.940 mmol), dropwise. The reaction mixture was allowed to warm slowly to ambient temperature and was stirred for 18 hours, then concentrated in vacuo. The residue was dissolved in MeOH (25 mL) and the resulting solution was stirred at ambient temperature for 18 hours. The solvent was evaporated under reduced pressure, and the residue was partitioned between saturated aqueous NaHCO3 (5 mL) and CHCl3 (20 mL). The aqueous layer was extracted further with CHCl3 (20 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with EtOAc—1% MeOH—0.1% NH4OH to yield the desired product as a pale foam.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in MeOH (25 mL)
  3. stirringthe resulting solution was stirred at ambient temperature for 18 hours
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was partitioned between saturated aqueous NaHCO3 (5 mL) and CHCl3 (20 mL)
  6. extractionThe aqueous layer was extracted further with CHCl3 (20 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash column chromatography on silica
  11. washeluting with EtOAc—1% MeOH—0.1% NH4OH

Sources & evidence

ORD record
ord-62c504a2eccb46c88486037095958ad1
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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