合成路线1

Cyanohydrin (II) was prepared by addition of KCN to 3,4-difluorobenzaldehyde (I) in the presence of sodium bisulfite. After protection of the hydroxyl group of (II) as the tetrahydropyranyl ether (III), alkylation with bromoethyl benzoate (IV) in the presence of LDA furnished adduct (V). Catalytic hydrogenation of the cyano group to give (VI), followed by tetrahydropyranyl group cleavage under acidic conditions, afforded amino alcohol (VII). Subsequent acylation of (VII) with chloroacetyl chloride produced the chloroacetamide (VIII). Intramolecular cyclization of (VIII) upon treatment with K2CO3 in boiling toluene yielded a racemic morpholinone that was resolved into the enantiomers by using L-tartaric acid. The desired (R)-morpholinone (IX) was then reduced to the corresponding morpholine (X) employing borane in THF.