| 主权项 |
1. A process for making compounds of Formula I the process comprising: (a) reacting the protected enamine of Formula III, wherein R2 is an enamine protecting group removable by catalytic hydrogenation, with a nitrating agent to form the corresponding protected nitro-enamine of Formula and subsequently reducing the product to a protected piperidine of Formula IV, wherein R2 is as defined above; (b) deprotecting the protected piperidine of Formula IV from step “a” by reacting it with hydrogen in the presence of a palladium catalyst to form the compound of Formula V, (c) alkylating the compound of Formula V by reacting it under Michael addition conditions with an acrylate of the formula 28a, to form the compounds of Formulae 27a and 27b, (c) precipitating a sulfonate salt of Formula 27a-sulfonate by reacting the compounds of Formula 27a and 27b formed in Step “c” with a sulfonic acid of the formula R5—SO3H, and (d) forming the lactam of Formula I by treating the compound of Formula 27a-sulfonate with acetic acid in the presence of zinc metal; wherein R5 is selected from benzyl, p-tolyl, and methyl and R1 is a linear, branched, or cyclic alkyl having up to 6 carbon atoms, phenyl, 2-methoxy-ethyl, 2-(dimethylamino)ethyl, (L)-menthyl, (D)-Menthyl, Dimethylamide, (R)-Benzyl -oxazolidinonamide, (S)-benzyl-oxazolidinonamide, isobornyl, cis-pinan-2-yl, isopinocamphenyl, adamantylmethyl, 2-adamantyl, 1-adamantyl, and (−)-8-phenylmenthyl. |
