Sodium Cyanide → HCID 59464394, compound

Participants

Reaction Steps

The preparation of Intermediate B3 followed the procedure by Horne et al. Heterocycles, 1994, 39, 139 incorporated herein by reference. A solution of (3-chloro-2-fluoro-phenyl)-acetaldehyde (Intermediate B2) (0.30 g, 4.57 mmol) in EtOH (7 mL) was treated with tosylmethyl isocyanide (TosMIC) (0.33 mg, 7.18 mmol) and NaCN (˜10 mg, cat.). The resulting mixture was allowed to stir at rt for 20 minutes. The solvent was removed in vacuo and the residue was dissolved in ˜7M NH3 in MeOH (35 mL) and transferred to a re-sealable tube. This mixture was heated in a re-sealable tube at 90-100° C. for 12 h. Thereafter the mixture was concentrated and purified by chromatography on SiO2 with 5% MeOH (sat. w/NH3):CH2Cl2 to give 5-(3-chloro-2-fluoro-benzyl)-1H-imidazole 0.4 g (31%) as an amber oil. The fumaric acid salt of the latter compound was formed in methanol and tetrahydrofuran. The solvent was removed and the salt was re-solvated in methanol:tetrahydrofuran and titurated with 20% ether-hexane. The solid was collected on a glass frit and dried under vacuum.

Provenance & Evidence