N-CYCLOPROPYLMETHYLTHIOUREA synthesis

Yield:618913-44-3 81%

Reaction Conditions:

with methanol;water;potassium carbonate at 20;

Steps:

94

Cvclopropylmethyl-thiourea; Add l-benzoyl-S-cyclopropylmethyl-thiourea (718 g, 3.06 mol) to methanol (6 L) and heat gently to dissolve. Add a solution of potassium carbonate (1.70 kg, 12.3 mol) in water (2 L) and stir overnight at room temperature. Filter any solids that form and concentrate the filtrate in vacuo until 10% of the volume. Dilute the residue with water (2 L) and EtOAc (-3.5 L) and extract the aqueous phase with EtOAc (4x2.5 L). Wash the combined organic extracts with aqueous IN NaOH (2x1 L) EPO and brine (2 L). Dry the organic layer over Na₂SO₄, filter, and concentrate in vacuo. Redissolve the residue in warm EtOAc (4 L), concentrate in vacuo until -20% of the volume and filter the precipitate, rinsing with cold (~5°C) EtOAc (~500 mL). Dry the solid under high vacuum to obtain the title compound as an off-white solid (220 g, 55%). Concentrate the filtrate in vacuo until -10% of the volume and filter the precipitate, rinsing with cold EtOAc. Dry the solid under high vacuum to provide a second crop of cyclopropylmethyl-thiourea as an off-white solid (103 g, 26%). Total yield (323 g, 81%). MS (APCI) m/z: 131 (M+H)⁺.

References:

WO2007/28083,2007,A2 Location in patent:Page/Page column 139-140