L-Dopa methyl ester hydrochloride

Methanol (50 ml) was cooled to -5° C. in a thermostatic bath, and thionyl chloride (5 ml, 68.9 mmol) was added dropwise. Then, 3, 4-dihydroxy-L-phenylalanine (10.0 g, 50.7 mmol) was added by small portions, and the mixture was stirred for 5 min. The mixture was warmed to room temperature, heated to 50° C., and stirred for 14 hr. The reaction solution was concentrated to give DOPA-OMe hydrochloride (14.3 g, 57.7 mmol, yield quant.) as an oil. (0195) Methanol (50 ml) was cooled to -5° C. in a thermostatic bath, and thionyl chloride (5 ml, 68.9 mmol) was added dropwise. L-DOPA methyl ester hydrochloride (2, DOPA-OMe). SOCl2 (5.0 mL, 70 mmol) was added slowly to dryMeOH (20 mL) at 5 °C. L-DOPA (1) (1.00 g, 50 mmol) was added to the reaction mixture. The reactionmixture was stirred at rt for 1 h and refluxed at 85 °C for 1 h. After the reaction, the reaction mixturewas concentrated to afford a colorless amorphous mass (1.24 g, 100percent). 1H-NMR (270 MHz, CD3OD)ppm: 6.75 (d, J = 8.2 Hz, 1H), 6.66 (d, J = 2.0 Hz, 1H), 6.55 (dd, 1 H, J = 8.1, 2.1 Hz, 1H), 4.21 (dd, J = 7.4, 5.8 Hz, 1H), 3.82 (s, 3H), 3.11 (dd, J = 14.5, 5.9 Hz, 1H), 3.00 (dd, J = 14.5, 7.3 Hz, 1H); 13C-NMR(68 MHz, CD3OD) ppm: 170.4, 146.7, 146.1, 123.3, 121.9, 117.3, 116.9, 55.4, 53.6, 36.7; HRMS (ESI) m/z[M + H]+ calcd. for C10H14NO4 212.0923, found 212.0928; []D = + 12 (c 1.0, CH3OH); UV (CH3OH):max = 283 (2788).Thionyl chloride (13.5mL, 184 mmol) was added dropwise to a solution of LDOPA1 (4.02 g, 20.4 mmol) in methanol (100 mL) at 0 °C .After 21 hours at room temperature, the solvent was evaporated, and the residue was concentrated to afford pale yellowmass (5.01 g, 99percent). 1H NMR (CD3OD): 3.00 (dd, J = 14.5, 7.3 Hz, 1H), 3.11 (dd, J = 14.5, 5.9 Hz, 1H), 3.82 (s, 3H), 4.21 (dd, J = 7.3, 5.9 Hz, 1H), 6.55 (dd, J = 8.2, 2.0 Hz, 1H), 6.66 (d, J = 2.0 Hz, 1H), 6.75 (d, J = 8.2 Hz, 1H); 13C NMR(CD3OD): 36.7, 53.6, 55.4, 116.9, 117.3, 121.9, 126.3, 146.1, 146.7, 170.4; HRMS (ESI): calcd. for C10H14NO4(M++H) 212.0923, found 212.0928; []D +9.8 (c 2.0, CH3OH).To an ice-cold suspension of L-DOPA (1.0 g, 5.07mmol) in MeOH (20 mL), SOClTo a solution of L-dopa (10.0 g, 50.7 mmol) in MeOH(300 mL) was added thionyl chloride (11.1 mL, 152 mmol)dropwise. The mixture was heated to reflux temperature for8 h. After the solution was cooled to room temperature, thesolvent was evaporated in vacuo to obtain the title compoundas a white foam (12.0 g, 95.2percent). 1H-NMR (dimethyl sulfoxide(DMSO)-d6) δ: 2.88–2.95 (1H, m), 2.98–3.04 (1H, m), 3.64 (3H, s), 4.04–4.10 (1H, m), 6.45–6.50 (1H, d), 6.40–6.50(1H, d, J=8.0 Hz), 6.59 (1H, s), 6.66–6.70 (1H, d, J=7.6 Hz);13C-NMR (DMSO-d6) δ: 35.34, 52.55, 53.45, 115.64, 116.55, 119.98, 124.67, 144.42, 145.06, 169.18.The methanol-free accurate amount of 5 ml in the round-bottom flask, ice-bath cooling 15 min, added slowly dropwise SOClSOCl2 (947 mL, 12.7 mmol) was added to anhydrous MeOH (18mL) in an ice bath. After 30 min, L-3, 4-dihydroxyphenylalanine(1.00 g, 5.07 mmol) was added, and the mixture was stirred atroom temperature for 56 h. After removal of the solvent, the residuewas purified by silica gel chromatography (CHCl3:MeOH =14:1) to afford L-DOPA methyl ester hydrochloride (a, 1.03 g, 93percent) as a white powder.General procedure: To 4mL of ice-bath cooled methanol was added drop-wise 1mL of thionyl chloride in 5min under nitrogen, the resulting mixture was stirred for 0.5h and amine derivatives 3a-3f were added. The reaction mixture was stirred at room temperature overnight until complete disappearance of the materials indicated by TLC. The solvent and the surplus SOCl