An Efficient Synthesis of a Key Inter- mediate for Vasopressin V2 Receptor Agonist OPC-51803 by Lipase-catalyzed Enantioselective Transesterification

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An efficient and enantioselective synthesis of (R)-[1-(p-toluene-sulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]acetic acid (2), a key intermediate in the synthesis of (R)-2-{1-[2-chloro-4-(1-pyrrolidinyl)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl}-N-isopropylacetamide (OPC-51803, 1), was accomplished. The chiral alcohol [(S)-3], the precursor of (R)-2, was separated from the racemic alcohol [(′)-3] using the lipase mediated transesterification in vinyl acetate. The obtained (S)-3 was fractionated without using column chromatography and it was converted to 2 without a decrease in the enantiomeric excess.