Hydrochloric Acid → Benzyl (3S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate--hydrogen chloride (1/1)

Participants

Reaction Conditions

Reaction Steps

To a suspension of crude (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid benzyl ester (example 5) (335 g, 0.7836 mol) in ethyl acetate (335 mL) and toluene (335 mL) was added 20% HCl solution in IPA (357 g, 1.959 mol) at 15-20° C. The reaction mixture then was heated to 40° C. over 1-2 h, and stirred at this temperature for 2 h. A 20% HCl solution in IPA (71.4 g, 0.3918 mol) was added, and the stirring was continued for another 2 h. The reaction mixture was cooled to 15-20° C., and stirred at this temperature. The mixture was filtered, and washed with ethyl acetate (2×670 mL). The white solids were dried under vacuum at 40° C. to give 278.6 g (99% yield, ee=98%) of (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid benzyl ester, hydrochloride. 1H NMR (DMSO-d6) δ: 3.10 (dd, J=16.64, 10.74 Hz, 1H, CHHCHCOOH), 3.24 (dd, J=16.64, 5.10 Hz, 1H, CHHCHCOOH), 3.72 (s, 6H, OCH3), 4.23 (br s, 2H, CH2N), 4.58 (dd, J=10.74, 5.10 hz, 1H, CHCOOH), 5.27 (d, J=12.48 Hz, 1H, PhCHH), 5.33 (d, J=12.48 Hz, 1H, PhCHH), 6.85 (br s, 2H, PhH), 7.35-7.46 (m, 5H, PhHCH2), 10.19 (br s, 2H, NH.HCl).

Provenance & Evidence