Yield:-

Reaction Conditions:

Stage #1: 1-(Acetylthiomethyl)cyclopropaneacetonitrilewith methanol;sodium methylate at 10; for 3 h;
Stage #2: with water;acetic acid in toluene at 0 - 5; pH=~ 4;

Steps:

19

EXAMPLE 19: PREPARATION OF (I-MERCAPTOMETHYL-CYCLOPROPYL)- ACETONITRILE (FORMULA XIV):1-(acetylthiomethyl)-cyclopropaneneacetonitrile (33 kg) and methanol (82 liters) were taken into a reactor and cooled to 10 ⁰C. Sodium methoxide solution of concentration of about 20% (58.3 kg) was added slowly into the reaction mass at about 10 ⁰C followed by addition of methanol (42 liters). The reaction mass was maintained at 10 ⁰C for about 3 hours and decomposed slowly by addition of water (330 liters). N- heptane (165 liters) was then added followed by stirring for about 15 minutes at 30 ⁰C. Separated the layers and washed the aqueous layer with 4x165 L of n-heptane. The aqueous layer was taken into a fresh reactor containing toluene (198 liters). Cooled the reaction solution to 0 ⁰C, and then pH of the reaction mass was adjusted to about 4 with acetic acid (42 liters) at below 5 ⁰C. The organic layer was separated and the aqueous layer was extracted into toluene (2x132 liters). The combined organic layer was washed with sodium bicarbonate solution (6.6 kg of sodium bicarbonate dissolved in 132 L of water) in two equal lots followed by washing with water (3^χ132 liters). The separated organic layer was treated with activated carbon (4.95 kg) and maintained for about 30 minutes. Filtered the reaction mass through a leaf filter and washed the cake with toluene (66 liters). The reaction solution was distilled off completely under vacuum to 80% of the original volume. The obtained residue was cooled to about 30 °C and charged into an agitated thin film evaporator followed by heating to 55⁰C under a vacuum of 700 mmHg. The obtained crude was cooled to 30 ⁰C to obtain 18.4 liters of EPO title compound. The obtained title compound was stored at below 5 ⁰C under a nitrogen atmosphere in a dry condition. Purity by GC: 84.76%.

References:

WO2008/58118,2008,A2 Location in patent:Page/Page column 37-38