Aluminium lithium hydride → HCID 57781141, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(2,3,3-trimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester (190 mg, 0.367 mmol) in THF (5.5 mL) at −25° C. is added lithium aluminum hydride (18 mg, 0.48 mmol). The reaction is permitted to warm to 0° C. over 2 h and the reaction is stirred for an additional 30 min at 0° C. After a total of 2.5 h the reaction is quenched at 0° C. by the consecutive addition of 9:1 THF/H2O (0.225 mL), 2M aqueous NaOH (0.090 mL), and H2O (0.170 mL). The reaction is warmed to room temperature and diluted with THF (2.0 mL). After addition of MgSO4 (250 mg), the heterogeneous mixture is stirred for 15 min and then filtered through a pad of Celite. The pad of Celite is washed with ethyl acetate and the combined filtrate is concentrated in vacuo. The resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 49:1 to 9:1) to afford 4-(5-hydroxymethyl-imidazol-1-yl)-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one as a colorless foam. High resolution mass spectrum (ES+) m/z 286.1547 [(M+H)+; calculated for C16H20N3O2: 286.1556]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22 (s, 3 H), 1.36 (s, 3 H), 2.12 (br. s, 1 H), 3.11 (s, 3 H), 4.65-4.95 (m, 2 H), 5.33 (s, 1 H), 6.95 (s, 1 H), 7.31-7.36 (m, 1 H), 7.37 (s, 1 H), 7.43-7.54 (m, 2 H), 8.18-8.25 (m, 1 H).

Provenance & Evidence