A scalable method for the preparation of oxindole 8, a key intermediate en route to a serine palmitoyl transferase inhibitor, compound 1, is presented. A three-step, chromatography-free route has been designed that takes advantage of Buchwald’s palladium-catalyzed C–H functionalization to cyclize an α-chloroacetanilide to form the five-membered ring. This process has been successfully carried out in our kilogram laboratory facility on 10-kg scale in 76% yield.

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A convergent route to multigram quantities of a mineralocorticoid antagonist 3 is described. Starting from (R)phenylglycinol, the synthesis of cis 2,5-morpholine 2 is accomplished utilizing a de-epimerization to install the second stereogenic center. The multigram synthesis of 3 was completed through a sequence of an S N Ar reaction, Dakin oxidation, alkylation, and cyclization to provide a crystalline solid.

Methyl 4‐aminobenzoate 1‐Benzyloxycarbonyl‐4‐piperidone Dichloromethane Acetic acid Sodium triacetoxyborohydride Benzyl 4‐(4‐(methoxycarbonyl)phenylamino)piperidine‐1‐carboxylate Benzyl 4‐(2‐chloro‐N‐(4‐(methoxycarbonyl)phenyl)acetamido)‐piperidine‐1‐carboxylate Pyridine Ethyl acetate Chloroacetyl chloride Methyl 1‐(1‐(benzyloxycarbonyl)piperidin‐4‐yl)‐2‐oxoindoline‐5‐carboxylate Palladium acetate 2‐(Di‐ t ‐butylphosphino)biphenyl 2‐Methyltetrahydrofuran 2‐Propanol Triethanolamine

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