Patent ID: 6482952
Filing Date: 2002-11-19
Classification: C07D

Abstract:
A process for preparing an acetonide of Formula (I): which comprises:(A) reacting an acid halide of Formula (II): with an alkoxy compound which is 2-alkoxypropene or 2,2-dialkoxypropane and an aminoalcohol of Formula (III): in the presence of LiOH and an ether as solvent, the reaction mixture having a single liquid phase, to form Compound I;whereinR1 is (1) hydrogen; (2) C1-C6 alkyl; (3) C1-C6 alkyl substituted with one or more substituents, each of which is independently hydroxy, cyano, or halo; (4) C3-C8 cycloalkyl; (5) C3-C8 cycloalkyl substituted with one or more substituents, each of which is independently C1-C4 alkyl, hydroxy, cyano, or halo; (6) aryl; (7) aryl substituted with one or more substituents, each of which is independently C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, hydroxy, cyano, halo, phenyl, â€”CO2Ra, â€”CORa, NRaRb, â€”NRaâ€”CORb, â€”NRbâ€”CO2Rb, â€”COâ€”NRaRb, â€”OCOâ€”NRaRb, â€”NRaCOâ€”NRaRb, â€”S(O)kRa wherein k is an integer from 0 to 2, â€”S(O)2â€”NRaRb, â€”NRaS(O)2â€”Rb, or â€”NRaS(O)2â€”NRaRb; (8) heterocycle; or (9) heterocycle substituted one or more substituents, each of which is independently C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, hydroxy, cyano, halo, phenyl, â€”CO2Ra, â€”CORa, â€”NRaRb, â€”NRaâ€”CORb, â€”NRbâ€”CO2Rb, â€”COâ€”NRaRb, â€”OCOâ€”NRaRb, â€”NRaCOâ€”NRaRb, â€”S(O)kRa wherein k is an integer from 0 to 2, â€”S(O)2â€”NRaRb, â€”NRaS(O)2â€”Rb, or â€”NRaS(O)2â€”NRaRb; R2a, R2b, R3a and R3b each independently have the same definition as R1; or R2a and R3a each independently have the same definition as R1, and R2b and R3b together with the carbon atoms to which each is attached form (1) a carbocycle; (2) a carbocycle substituted with one or more substituents, each of which is independently C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, hydroxy, cyano, halo, phenyl, â€”CO2Ra, â€”CORa, â€”NRaRb, â€”NRaâ€”CORb, â€”NRbâ€”CO2Rb, â€”COâ€”NRaRb, â€”OCOâ€”NRaRb, â€”NRaCOâ€”NRaRb, â€”S(O)kRa wherein k is an integer from 0 to 2, â€”S(O)2â€”NRaRb, â€”NRaS(O)2â€”Rb, or â€”NRaS(O)2â€”NRaRb; (3) a heterocycle; or (4) a heterocycle substituted with one or more substituents, each of which is independently C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, hydroxy, cyano, halo, phenyl, â€”CO2Ra, â€”CORa, â€”NRaRb, â€”NRaâ€”CORb, â€”NRbâ€”CO2Rb, â€”COâ€”NRaRb, â€”OCOâ€”NRaRb, â€”NRaCOâ€”NRaRb, â€”S(O)kRa wherein k is an integer from 0 to 2, â€”S(O)2â€”NRaRb, â€”NRaS(O)2â€”Rb, or â€”NRaS(O)2â€”NRaRb; each Ra and Rb is independently hydrogen or C1-C4 alkyl; X is halogen; and m is an integer from 0 to 5; wherein the carbocycle is a saturated or unsaturated monocyclic ring consisting of from 5 to 7 carbon atoms or a bicyclic ring consisting of from 7 to 10 carbon atoms in which either or both rings of the bicyclic are saturated or unsaturated; the aryl is an aromatic mono- and poly-carbocyclic ring system wherein the carbocyclic rings in the polyring system are either fused or attached to each other via single bonds; and each heterocycle is independently a (i) a 4- to 8-membered, saturated or unsaturated monocyclic ring consisting of carbon atoms and one or more heteroatoms selected from N, O and S or (ii) a 7- to 10-membered bicyclic ring system, either ring of which is saturated or unsaturated, consisting of carbon atoms and one or more heteroatoms selected from N, O and S; and wherein the nitrogen and sulfur heteroatoms in (i) or (ii) are optionally oxidized, and the nitrogen heteroatom is optionally quaternized.