Water → HCID 12108676, compound

Participants

Reaction Conditions

Reaction Steps

Benzyl chloride (116.4 g, 0.92 mol), powdered K2CO3 solids (87 g, 0.63 mol), NaI (6.0 g, 0.04 mol) and Bu4N+Br− (1.5 g, 0.0046 mol) were added to a solution of crude compound (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid (297 g, 0.8357 mol) in DMF (890 mL) at 20-25° C. The reaction mixture was stirred at 40-50° C. for 5 h. The reaction mixture then was cooled to 0-5° C., and water (1.78 L) was added in portions (IT<20° C.). The resulting light yellow suspension was stirred at 5-15° C. The mixture was filtered and washed with water (2×600 mL) and heptane (600 mL). The off-white solids were dried under vacuum at 45° C. to afford crude (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid benzyl ester (335 g, 93.8% yield). 1H NMR (DMSO-d6) δ: 1.35, 1.45 (s, 9H, C(CH3)3), 2.93-3.18 (m, 2H, CH2CHCOOH), 3.17 (s, 6H, OCH3), 4.30 (d, J=16.15 Hz) and 4.37 (d, J=16.40 Hz, minor rotamer) (1H, CHHN), 4.45 (d, J=16.15 Hz) and 4.52 (d, J=16.40 Hz, minor rotamer) (1H, CHHN), 4.68 (dd, J=5.4, 4.3 Hz) and 4.90 (dd, J=5.9, 2.2 Hz, minor rotamer) (1H, CHCOOH), 6.74, 6.78, 6.81 (s, PhH).

Provenance & Evidence