Patent ID: 6700001
Filing Date: 2004-03-02
Classification: C07D

Abstract:
A process for the stereoselective synthesis of a 2-hydroxymethyl-chroman comprising(a) providing an optically active benzene compound of formula (I), whereinR0 is hydrogen or an oxygen protecting group, R is an oxygen protecting group or hydrogen, or the moiety OR is a leaving group, and R1, R2 and R3 are independently selected from hydrogen, a halogen atom, a cyano, azido, nitro, hydroxyl, carboxyl, acyl or carboxamido group, a C1 to C6 alkyl group, a 5- to 7-membered aromatic group optionally having as ring members up to 2 heteroatoms independently selected from O, N or S, a C5 to C7 membered aryloxy group, a C1, to C6 alkoxy group, a C2 to C7 alkenyl group, a carboalkoxy group having 1 to 6 carbon atoms in the alkyl chain, alkanamido group having 1 to 6 carbon atoms in the alkyl chain, alkanesulfonamido group having 1 to 6 carbon atoms in the alkyl chain, an alkanoyloxy group having 1 to 6 carbon atoms in the alkyl chain, a perhalogenated C1 to C6 alkyl or alkoxy group, an amino group or a mono- or di-alkylamino having 1 to 6 carbon atoms per alkyl chain, or two of R1, R2 or R3, taken together, form a 5- to 7-membered saturated, partly saturated, unsaturated, or aromatic carbocyclic or bridged carbocyclic ring, wherein the ring may i) optionally have up to two ring atoms selected from S, N, or O, ii) optionally have as a ring member up to 2 carbonyl groups or iii) optionally be substituted by 1 to 2 R5 substituents where each R5 substituent is independently selected from a halogen atom, a cyano, nitro or hydroxyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a 5- to 7-membered aromatic group optionally having 1-2 ring atoms selected from N, O or S, or in spiro form a carbocyclic ring having 5 to 7 carbon atoms, or any combination of i), ii) or iii); (b) if R0 is not H, deprotecting the OR0 moiety of formula (I) to produce a phenol compound of formula (IA) (c) reacting the phenol of formula (IA) in one or more reactions to form a 2-hydroxymethyl-chroman of formula (II) wherein at least one of the reactions is a stereospecific cyclization reaction.