Process for the preparation of (S,S)-CIS-2-phenyl-3-aminopiperidine

A process for preparing (S,S)-cis-2-phenyl-3-amino-piperidine which comprises:

• (a) reacting the amino acid, L-ornithine or salt having a protecting group on the amino group on the α-carbon and the amino group on the δ-carbon thereof, having the formula
• 7
• with N-methoxy-N-methylamino or salt thereof under amide forming conditions to produce an amide of the formula in the S configuration
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• (b) adding said amide to an effective amount of a Grignand reagent of the formula Ph MgX to form a ketone of the formula in the S configuration
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• (c) selectively deprotecting the amino group on the δ carbon under conditions sufficient to cyclize said ketone to form a cyclic imine and reducing the resulting imine to form a product of the formula in the (S,S) configuration
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• (d) removing the protecting group on the α-carbon to form said (S,S)-cis-2-phenyl-3-aminopiperidine, wherein
• P1 and P2 are different amino protecting groups, which are removed under different reaction conditions and
• X is halide.