1-(isothiocyanatomethyl)-2-methoxybenzene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (±)-[4-chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (76 mg, 0.20 mmol, 1.0 eq.) and N-ethyldiisopropylamine (42 μL, 0.24 mmol, 1.2 eq) in DCM (2 mL), 2-methoxybenzyl isothiocyanate (36 mg, 0.20 mmol, 1.0 eq.) was added. The resulting mixture was stirred at r.t. for 19 hours. The mixture was diluted with DCM (20 mL), washed with 10% aq. AcOH (2×5 mL) and with sat. aq. NaCl (1×5 mL). The org. layer was concentrated in vacuo. The residue was dissolved in DMF (1 mL). 1M aq. NaOH soln. (0.5 mL) was added. The mixture was stirred at r.t. for 7 hours. The solution was carefully neutralized with formic acid (0.5 mL), filtered, and purified by prep. HPLC (column: Waters X-bridge, 30×75 mm, 10 um, UV/MS, acidic conditions) to give the desired acid as a white solid. washed with 10% aq. AcOH (2×5 mL) and with sat. aq. NaCl (1×5 mL) layer was concentrated in vacuo The residue was dissolved in DMF (1 mL) (0.5 mL) was added The mixture was stirred at r.t. for 7 hours filtered purified by prep

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (±)-[4-chloro-2-(4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-4-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (50 mg, 0.13 mmol, 1.00 eq.) and NEt3 (54 μL, 0.39 mmol, 3.00 eq.) in MeCN (1 mL), 2-methoxybenzyl isothiocyanate (24 mg, 0.14 mmol, 1.05 eq.) in MeCN (1 mL) was added. The mixture was stirred at r.t. for 18 hours. 1M aq. NaOH (0.5 mL) was added. The mixture was stirred at r.t. for 18 hours. The solution was neutralized with formic acid, purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions), and concentrated in vacuo to give the desired acid as a white solid. The mixture was stirred at r.t. for 18 hours purified by prep HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions), and concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxybenzylamine (1.80 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml), extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-methoxybenzyl)isothiocyanate (2.35 g, yield: 99%) as brown oil. extracted with diethylether (60 ml) dried over anhydrous magnesium sulfate concentrated under reduced pressure