Cesium carbonate → 5-Bromo-4-chloro-2-ethyl-1-(2,2,2-trifluoroethyl)-1H-benzimidazole

HRID 1188493Notes

Reaction equation

[Br:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7]([CH2:9][CH3:10])=[N:8][C:4]=2[C:3]=1[Cl:13].O([CH2:22][C:23]([F:26])([F:25])[F:24])S(C(F)(F)F)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Br:1][C:2]1[CH:12]=[CH:11][C:5]2[N:6]([CH2:22][C:23]([F:26])([F:25])[F:24])[C:7]([CH2:9][CH3:10])=[N:8][C:4]=2[C:3]=1[Cl:13]

Participants

Conditions

Temperature: 90 °C

Procedure

5-Bromo-4-chloro-2-ethyl-1H-benzimidazole (0.049 g, 0.188 mmol), trifluoroethyl triflate (0.065 g, 0.282 mmol), and Cs2CO3 (0.092 g, 0.282 mmol) were combined in DMF (5 mL) and the resulting solution was heated to 90° C. for 30 min. The reaction mixture was partitioned between H2O and Et2O and further extracted with Et2O. The combined organic portions were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Chromatography (SiO2, EtOAc/hexanes) allowed separation of the regioisomers. 0.083 g of desired regioisomer was isolated: 1NMR (400 MHz, CDCl3) δ 7.5 (d, J=8.5 Hz, 1H), 7.2 (d, J=8.5 Hz, 1H), 4.6 (q, J=8.3 Hz, 2H), 2.9 (q, J=7.4 Hz, 2H), 1.45 (t, J=7.4 Hz, 3H); MS (ESI) m/z 343 (M+1).

Workup

customThe reaction mixture was partitioned between H2O and Et2O
extractionfurther extracted with Et2O
washThe combined organic portions were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customseparation of the regioisomers
custom0.083 g of desired regioisomer was isolated

Sources & evidence

ORD record: ord-32b582428ca242938e79c4ee290a3f9e
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673948B2

Reaction notes

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