Expedient Synthesis of 4(5)-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole, the α₂-Adrenergic Agonist Medetomidine

Stereomeric Pyrrolidinopentoses Bearing an Imidazole Ring − Synthesis, Chiroptical Properties, and Evaluation as Potential Sugar-Mimic Glycosidase Inhibitors

“…The starting material was the -erythro compound 22, a known and easily prepared product. [16,17] Nucleophilic addition of the known lithio derivative of imidazole 23 [18] to 22 provided the minor -arabino product 24 (25%) and the major -ribo diastereomer 25 (75%) in 88% overall yield. Adduct 25 was O-benzylated and the acid-sensitive protection groups of the ensuing (fully protected) intermediate were removed with HCl, to afford ent-18.…”

“…13 to a stirred solution of imidazole 23 (6.05 g, 20.9 mmol) in anhydrous THF (50 mL), whereupon the solution became red. After 15 min, a solution of the known compound 22 (4.25 g, 17.0 mmol) [17,18,21] in anhydrous THF (40 mL) was added dropwise, and the reaction mixture was monitored by TLC (EtOAc/cyclohexane, 3:7). After 90 min, the solution was allowed to warm to room temp., H 2 O (30 mL) was added, the reaction mixture was extracted with CH 2 Cl 2 , and the organic phase was dried (MgSO 4 ), filtered, and concentrated to dryness to afford an orange-colored syrup that consisted of the two diastereomers 24 (minor product) and 25 (major product) in a 1:3 ratio.…”

Stereoisomeric Imidazolo-Pentoses − Synthesis, Chiroptical Properties, and Evaluation as Glycosidase Inhibitors

“…[14,15] in anhydrous THF (35 mL) at Ϫ78°C was added dropwise a 1.6  solution of nBuLi in hexane (8.0 mmol, 1.2 equiv.). After 25 min at Ϫ78°C, the reddish solution was allowed to warm to Ϫ50°C.…”

Synthesis and Enantiomeric Resolution of Medetomidine

“…[3][4][5] Several syntheses of medetomidine have been reported. [6][7][8][9][10][11][12][13] The first method for the preparation of 5 and of other related 4-benzylimidazoles was described in a patent starting from 2,3-dimethylbromobenzene as shown in Scheme 1; unfortunately the yields were not reported. [6][7][8] A second route, proceeding in 41% overall yield (Scheme 2), 9 also involved the reaction of the Grignard reagent derived from 1 with 4-(1-triphenylmethyl)imidazole carboxaldehyde (6).…”

“…In a third preparation, secondary carbinol 7 was obtained via the addition of 2,3-dimethylbenzaldehyde (10) to the Grignard reagent prepared from 4-iodo-(1-tripheny1-methyl)imidazole (11). Subsequent oxidation with MnO 2 , addition of MeMgCl, deprotection and hydrogenolysis afforded 5 in »60% overall yield (Scheme 3).…”