Classical and dynamic resolution of 1-amino-3-methyl-1,3,4,5-tetrahydrobenzo[d]azepin-2-one

Two efficient production processes of enantioenriched 1-amino-3-methyl-1,3,4,5-tetrahydro-benzo[d]azepin-2-one 1 were achieved using the readily available starting materials. A key step in the methodologies is a classical resolution or a dynamic resolution that provides excellent chemical (>80%) yields and enantiomeric excesses (>99.8% ee). The classical resolution was developed on a preparative scale while the dynamic resolution was implemented on a pilot plant scale.

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(1S)-1-Amino-3-methyl-1,3,4,5-tetrahydro-benzo[d]azepin-2-oneC11H14N2OEe = 100%[α]D24=+56 (c 1.50, CH3OH)Source of chirality: mandelic acidAbsolute configuration: (1S)