Hydrochloric Acid → [(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]acetaldehyde

Participants

Reaction Steps

A 1:1 solution of dioxane:3N HCl was added to a flask containing (3R)-6-(1,3-dioxolan-2-ylmethyl)-3-methyl-3,4-dihydro-1H-isochromen-1-one (782 mg, 3.15 mmol). The reaction was then stirred at room temp overnight. The crude reaction mixture was then partitioned between water and DCM. The organic layer was washed with saturated sodium bicarbonate solution, followed by brine. The organic layer was then dried with mag. sulfate, filtered and concentrated to afford [(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]acetaldehyde. The crude aldehyde was redissolved in DCM. To the solution was added Boc-piperazine (671 mg, 3.6 mmol) followed by sodium triacetoxyborohydride (1.91 g, 9.0 mmol). The reaction mixture was allowed to stir overnight before being quenched with 10 mL of MeOH. The excess solvent was removed and the residue was re-redissolved in DCM; washed with water and brine, dried with magnesium sulfate, filtered, concentrated and purified via MPLC (50-100% EtOAc/Hex) to afford tert-butyl 4-{2-[(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]ethyl}piperazine-1-carboxylate. 1H NMR (500 MHz; CDCl3): 8.02 (d, J=7.8 Hz, 1H), 7.24 (d, J=7.7 Hz, 1H), 7.09 (s, 1H), 4.68 (m, 1H), 3.49 (m, 4H), 2.94 (m, 4H), 2.88 (m, 2H), 2.51 (m, 4H), 1.54 (d, J=6.8 Hz, 3H), 1.48 (s, 9H); LC-MS (IE, m/z): 375 [M+1]+;

Provenance & Evidence