Yield: 88%

Reaction Conditions:

with calcium carbonate in hydrogenchloride;dichloromethane;water

Steps:

47.6 (Step 6)
(Step 6) Synthesis of 5-fluoro-2-methylphenyl isothiocyanate Under stirring at 0?C, a solution of 5-fluoro-2-methylaniline (1.23 g, 9.84 mmol) in methylene chloride (10 ml) was added dropwise to a mixture of calcium carbonate (2.46 g, 24.6 mmol) and thiophosgene (750 ?l, 9.84 mmol) in a methylene chloride/water (1/1, 40 ml) mixture. After completion of the dropwise addition, the reaction mixture was stirred further at 0?C for 35 minutes. The reaction mixture was poured in ice-1N HCl, followed by extraction with chloroform. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent to give 5-fluoro-2-methylphenyl isothiocyanate (1.45 g, 88%) as a brown oil. MS (ESI) m/z 167 (M⁺).

References:

DAIICHI PHARMACEUTICAL CO., LTD. EP1346982, 2003, A1