Hydrochloric Acid → Arbaclofen Hydrochloride

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, methyl (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylate (5.00 g, 19.7 mmol) was suspended in 1,2-dichlorobenzene (25 ml), and the suspension was dropped over a period of about 3 hours into 6 mol/L hydrochloric acid (20 g) heated up to 100° C. The mixture was reacted for 10 hours, then, cooled to 80° C., and the organic layer was separated by a liquid-separation operation. The aqueous layer was concentrated under reduced pressure, acetonitrile (15 ml) was added, and the mixture was concentrated again, then, acetonitrile (30 ml) was added, and the mixture was stirred at room temperature for 1 hour. The crystal was filtrated and washed with acetonitrile (5 ml) to obtain 4.00 g (16.0 mmol) of a title compound (yield: 81%). The spectrum data corresponded to the value in Example 4. The optical purity of the resultant title compound was measured by HPLC to find a value of 99.9% ee.

Provenance & Evidence