Lithium hydroxide, monohydrate → HCID 57781076, compound

Participants

Reaction Steps

To a solution of 2-cyclopropyl-3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline-4-carboxylic acid (4.1 g, 15.8 mmol) in acetic acid (300 mL) is added benzene (150 mL), potassium acetate (10.9 g, 111 mmol), cupric acetate (0.145 g, 0.8 mmol) and lead (IV) acetate (12.7 g, 28.6 mmol). The green reaction mixture is heated to reflux for 2.5 h. The reaction mixture is then cooled to room temperature and quenched by the addition of ethylene glycol (ca. 6 mL). The resulting solution is the concentrated in vacuo to near dryness. The resulting dark green oil is dissolved in ethyl acetate (ca. 500 mL) and stirred vigorously while cautiously treating with saturated aqueous sodium bicarbonate (ca. 200 mL), followed by solid NaHCO3 until the aqueous layer reached a pH greater than 8. The layers are separated and the aqueous layer is extracted three times with ethyl acetate. The organic layer is dried with Na2SO4 filtered and concentrated. The resulting brown oil is then dissolved in THF (150 mL). Water (30 ml) and LiOH H2O (3.5 g, 83.4 mmol) are added. The reaction mixture is placed at 45° C. for 18 h, whereupon it is cooled to room temperature. The reaction is concentrated in vacuo to ca. ¾ of its original volume, diluted with methylene chloride and saturated aqueous NaHCO3. The layers are separated and the aqueous layer is extracted three times with ethyl acetate. The organic layers are combined, dried with Na2SO4, filtered and concentrated in vacuo to afford a brown oil. Purification by silica gel flash chromatography (ethyl acetate-dichloromethane, 1:19 to 1:4) gave 2-cyclopropyl-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one as an off-white solid; MS (ESI) m/z 232.1 (M+H).

Provenance & Evidence