[C:1](=[S:3])=S.[NH2:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([Cl:14])[CH:6]=1.C(N(CC)CC)C.II.Cl.S([O-])([O-])=O.[Na+].[Na+].C(=O)([O-])O.[Na+]>O.C(OCC)(=O)C.O1CCCC1>[N:4]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([Cl:14])[CH:6]=1)=[C:1]=[S:3]Carbon disulfide (0.26 mL, 4.4 mmol) was added to a mixture comprising 4-amino-2-chlorobenzoic acid (0.26 g, 1.5 mmol), tetrahydrofuran (1.0 mL), water (1.0 mL) and triethylamine (0.51 mL, 3.6 mmol), followed by stirring at room temperature for 24.5 hours. To the obtained reaction mixture, a tetrahydrofuran (1.0 mL) solution of iodine (0.41 g, 1.6 mmol) was dropwise added over a period of 5 minutes at 0° C., followed by stirring at 0° C. for further two hours. Thereafter, 1M hydrochloric acid (1.5 mL) and sodium sulfite (38 mg, 0.30 mmol) were added and stirred. Then, ethyl acetate (6 mL) was added, and the organic layer was separated and concentrated under reduced pressure to dryness. To the residue, water (4 mL) and sodium hydrogencarbonate (0.14 g, 1.7 mmol) were added, and the insoluble matter was removed by filtration. To the filtrate, 1M hydrochloric acid (1.5 mL) and water (2.0 mL) were added, and the precipitated solid was collected by filtration. To this solid, ethyl acetate (6 mL), water (2.0 mL) and sodium hydrogencarbonate (25 mg, 1.7 mmol) were added, and the organic layer was concentrated under reduced pressure to dryness to obtain 4-isothiocyanato-2-chlorobenzoic acid as a white solid (0.20 g, yield: 62%, HPLC purity: 91%, HPLC retention time: 3.9 min). LC-MS ES-212, 214 (retention time: 4.2 min, condition 1).
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