Reaction #49161

Reaction equation

H2O

2-bromo-1-(4-bromophenyl)ethanone

N-Boc-L-Valine

iPr2NEt

CH3CN

→

title compound

Yield 94.0%

(S)-tert-butyl 1-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-methylpropylcarbamate

Yield 94.0%

Solvents

toluene

Conditions

Workup

1. 1
   OtherThe solvent was removed in vacuo
2. 2
   Otherthe resulting slurry was partitioned between EtOAc and H2O
3. 3
   OtherThe layers were separated
4. 4
   Extractionthe aq phase was extracted with EtOAc
5. 5
   DryingThe combined organic layers were dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   Otherto give a yellow oil
9. 9
   TemperatureThe mixture was heated
10. 10
    TemperatureThe mixture was cooled to rt
11. 11
    Concentrationconcentrated to dryness in vacuo
12. 12
    OtherThe residue was purified column chromatography (biotage)
13. 13
    Washeluting with 10% MeOH in CH2Cl2

Procedure

A solution of 2-bromo-1-(4-bromophenyl)ethanone (6.23 g, 22.3 mmol) and N-Boc-L-Valine (5.00 g, 23.0 mmol) in dry CH3CN (30 mL) was treated with iPr2NEt (4.40 mL, 25.3 mmol) and the solution was allowed to stir at rt overnight. The solvent was removed in vacuo and the resulting slurry was partitioned between EtOAc and H2O. The layers were separated and the aq phase was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a yellow oil. LCMS: Anal. Calcd. for C18H24BrNO5: 413, 415; found: 412, 414 (M−H)−. The residue was suspended in toluene (60 mL) and NH4OAc (8.61 g, 111.7 mmol) was added. The mixture was heated reflux for 16 h with azeotropic removal of H2O (Dean-Stark). The mixture was cooled to rt and concentrated to dryness in vacuo. The residue was purified column chromatography (biotage) eluting with 10% MeOH in CH2Cl2 to afford the title compound (8.55 g, 94%) as a yellow foam. 1HNMR (500 MHz, CD3OD) δ 7.84 (s, 1H), 7.66 (app d, J=8.9 Hz, 2H), 7.64 (app d, J=8.9 Hz, 2H), 4.65 (d, J=7.7 Hz, 1H), 2.23-2.27 (m, 1H), 1.42 (s, 9H), 1.07 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H). LCMS: Anal. Calcd. for C18H24BrN3O2: 393, 395; found: 394, 396 (M+H)+.

Source