Acetone → Sembragiline

Participants

Reaction Steps

In the reaction flask, (S)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one (7.0 g, 23.3 mmol), prepared as described in the previous example, was charged together with dichloromethane (70 mL). At 40° C., a solution of acetic anhydride (2.97 g, 29.1 mmol) in dichloromethane (10 mL) was added dropwise under stirring over 30 min. After a reaction time of 1.5 h, no starting material was left according to HPLC. Acetone (250 mL) was added and the mixture was concentrated in vacuo to a volume of ˜50 mL. The residue was dissolved in acetone (250 mL) at 60° C. The warm solution was treated with charcoal, the resulting suspension filtered and the charcoal washed with warm acetone. The filtrate was concentrated at 60° C. to a volume of ˜50 mL when the product started to crystallize. At room temperature, tert-butyl methyl ether (100 mL) was added and the suspension was kept at this temperature overnight. The crystals were collected by filtration, washed with tert-butyl methyl ether and dried in vacuo to afford (S)—N-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetamide (7.0 g, 88%) as an off-white powder. The purity of the material by HPLC was 99.4% (area) and the enantiomeric ratio (S):(R) was determined as >99.9:0.1. The result of the elemental analyses (C,H,N,F,O) corresponded to the expected values.

Provenance & Evidence