Lithium hydroxide, monohydrate → HCID 10655326, compound

Participants

Reaction Steps

To a solution of 3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline-4-carboxylic acid (5.0 g, 22.8 mmol) in acetic acid (450 mL) and benzene (160 mL) is added successively, potassium acetate (15.7 g, 160 mmol), cupric acetate (210 mg, 1.14 mmol), and lead (IV) acetate (18.2 g, 41.1 mmol). The green solution is heated to reflux for 4 h, at which time additional lead (IV) acetate (2.0 g 4.5 mmol) is added. After a total of 5 h at reflux the reaction is cooled to room temperature and quenched by the addition of ethylene glycol (ca. 5 mL). The reaction is concentrated in vacuo to near dryness. The resulting dark green oil is dissolved in ethyl acetate and stirred vigorously while cautiously treating with saturated aqueous sodium bicarbonate followed by solid NaHCO3 until the aqueous layer reached a pH greater than 8. The layers are separated and the aqueous layer is extracted 3 times with ethyl acetate. The organic layer is dried with Na2SO4 filtered and concentrated. The resulting brown oil is then dissolved in THF (200 mL). Water (40 ml) and LiOH.H2O (5.0 g, 118.6 mmol) are added. The reaction mixture is heated to 45° C. and stirred for 18 h, at which time 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 3 times with ethyl acetate. The organic layers are combined, dried with Na2SO4, filtered and concentrated in vacuo to afford a brown oil, which is pre-adsorbed on silica gel for further purification. Purification by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 23:2) furnished 4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one as an off-white foam; MS (ESI) m/z 192.1 (M+H).

Provenance & Evidence