Methyl Glycolate → HCID 91307750, compound

HRID 2306277Notes

Reaction equation

HRID 2306277 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([C:35]1[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[C:37]([F:43])[CH:36]=1)([C:11]1[N:12]=[CH:13][N:14](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:15]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:44]([O:48][CH3:49])(=[O:47])[CH2:45]O.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]([NH:8][C:9]([C:11]1[N:12]([CH2:45][C:44]([O:48][CH3:49])=[O:47])[CH:13]=[N:14][CH:15]=1)([C:35]1[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[C:37]([F:43])[CH:36]=1)[CH3:10])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 66774Methyl GlycolateHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 70170495HCID 70170495, compound

Product 1

HCID 91307750HCID 91307750, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-(tert-butoxycarbonyl)-1-(4-cyano-3-fluoro-phenyl)-1-[1-(triphenylmethyl)imidazol-4-yl]ethylamine, as described above in Step B, (2.6 g, 4.5 mmol), methyl glycolate (532 mg, 5.9 mmol), and N,N-diisopropylethyl-amine (1.6 g, 11.7 mmol) in dry CH2Cl2 (100 mL), under argon, at −78° C., was added trifluoromethanesulfonic anhydride (1.7 g, 5.9 mmol) dropwise. The mixture was allowed to warm slowly to ambient temperature, then the solvent was removed in vacuo. The residue was dissolved in MeOH (50 mL) and the solution was heated to reflux for 1 hour, then concentrated to dryness. The residue was purified by silica gel chromatography, eluting with EtOAc—2% MeOH—0.2% NH4OH. The product was further purified by preparative HPLC using a C-18 column and eluting with a gradient of H2O—0.2% triethylamine—0.1% AcOH—0% to 60% CH3CN to yield the titled product.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in MeOH (50 mL)
  3. temperaturethe solution was heated
  4. temperatureto reflux for 1 hour
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with EtOAc—2% MeOH—0.2% NH4OH
  8. customThe product was further purified by preparative HPLC
  9. washeluting with a gradient of H2O—0.2% triethylamine—0.1% AcOH—0% to 60% CH3CN

Sources & evidence

ORD record
ord-064af6517ac24022b144f17a7b343d37
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

Loading…