Ammonium Acetate → (S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1945351Notes

Reaction equation

HRID 1945351 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][NH:10][C:11]([C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=O)=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:30]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:30][C:11]([C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 517165Ammonium AcetateHCID 56605334(S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate

Product 1

HCID 56605031(S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

Procedure

A mixture J.6 (S)-tert-butyl 2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-pyrrolidine-1-carboxylate (12.8 g, 31.12 mmol) and ammonium acetate (12.0 g, 155.7 mmol) in xylenes (155 mL) was heated in a sealed tube at 140° C. for 2 hours. The volatile component was removed in vacuo, and the residue was partitioned carefully between ethyl acetate and water, whereby enough saturated NaHCO3 solution was added so as to make the pH of the aqueous phase slightly basic after the shaking of the biphasic system. The layers were separated, and the aqueous layer was extracted with an additional ethyl acetate. The combined organic phase was washed with brine, dried (MgSO4), filtered, and concentrated. The resulting material was recrystallized from ethyl acetate/hexanes to provide two crops of J.7 (S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate, 5.85 g. The mother liquor was concentrated in vacuo and submitted to a flash chromatography (silica gel; 30% ethyl acetate/hexanes) to provide an additional 2.23 g. 1H NMR (DMSO-d6, δ=2.5 ppm, 400 MHz): δ 12.17/11.92/11.86 (m, 1H), 7.72-7.46/7.28 (m, 5H), 4.86-4.70 (m, 1H), 3.52 (app br s, 1H), 3.36 (m, 1H), 2.30-1.75 (m, 4H), 1.40/1.15 (app br s, 9H). LC (Cond.-J1): RT=1.71 min; LC/MS: Anal. Calcd. For [M+H]+ C18H23BrN3O2: 392.10; found 391.96. HRMS: Anal. Calcd. For [M+H]+ C18H23BrN3O2: 392.0974; found 392.0959.

Workup

  1. customThe volatile component was removed in vacuo
  2. customthe residue was partitioned carefully between ethyl acetate and water, whereby enough saturated NaHCO3 solution
  3. additionwas added so as
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with an additional ethyl acetate
  6. washThe combined organic phase was washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting material was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-53a1ed1c50b248318e9eaee6dd56f0ce
Source dataset
uspto-grants-2013_03
Patent number
US08394968B2

Reaction notes

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