O.Cl.[NH2:3][C@@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[C:13]#N.P([O-])([O-])([O-])=O.C([O-])(O)=O.[Na+]>CO>[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[C:13]1[S:6][CH2:5][C@H:4]([C:7]([OH:9])=[O:8])[N:3]=1D-cysteine hydrochloride monohydrate (6.8 g, 38.7 mmol) was added to a solution of 2,4dihydroxybenzonitrile (3.5 g, 25.9 mmol), prepared as described above, in a mixture of degassed methanol (105 ml) and 0.1 M phosphate buffer, pH 5.95 (70 ml). NaHCO3 (3.25 g, 38.7 mmol) was carefully added and the mixture was stirred at 70° C. under Argon for 54 hours. Volatile components were removed under reduced pressure and the solution was acidified with 1 N HCl to pH 2. The resulting brown precipitate was vacuum filtered and the solid was washed with water (40 ml) and ethanol (20 ml). The crude product was dissolved in saturated NaHCO3 (700 ml) and the aqueous solution washed with ethyl acetate (2×200 ml). The aqueous layer was filtered through a fine frit and acidified with 1 N HCl to pH 2. The precipitated product was vacuum filtered. The aqueous layer was extracted with ethyl acetate (4×400 ml), the combined organic extracts were dried (Na2SO4) and the solvent was removed in vacuo. The remaining solid was combined with the precipitated product and dried under high vacuum at 40° C. for 12 hours to give 4,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid (4.08 g, 66%), mp 266–268° C. (dec) (Ind. J. Chem., Vol. 15B, Kishore et al, pages 255–257 (1977) for (L)-isomer: 261–262° C.). 1H NMR (300 MHz, DMSO-d6) δ 3.61 (m, 2 H), 5.38 (dd, 1 H, J=7.2/9.4 Hz), 6.31 (d, 1 H, J=2.3 Hz), 6.38 (dd, 1 H, J=2.3/8.6 Hz), 7.25 (d, 1 H, J=8.6 Hz), 10.25 (br s, 1 H), 12.60 (br s, 1 H), 13.15 (br s, 1 H). Anal. Calc. For C10H9NO4S: C 50.20, H 3.79, N 5.85. Found: C 50.13, H 3.82, N 5.85.
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