A method of stereoselectively making an aminocyclohexyl ether comprises,
for example, reacting to form the aminocyclohexyl ether having the
formula respectively, wherein independently at each occurrence,
R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-C.sub.8alkyl,
C.sub.3-C.sub.8alkoxyalkyl, C.sub.1-C.sub.8hydroxyalkyl, or
C.sub.7-C.sub.12aralkyl; or R.sub.1 and R.sub.2 are independently
C.sub.3-C.sub.8alkoxyalkyl, C.sub.1-C.sub.8hydroxyalkyl, and
C.sub.7-C.sub.12aralkyl; or R.sub.1 and R.sub.2, when taken together with
the nitrogen atom to which they are directly attached in formula (57) or
(75), form a ring denoted by formula (I): wherein the ring of formula
(I) is formed from the nitrogen as shown as well as three to nine
additional ring atoms independently carbon, nitrogen, oxygen, or sulfur;
where any two adjacent ring atoms may be joined together by single or
double bonds, and where any one or more of the additional carbon ring
atoms may be substituted with one or two substituents selected from the
group consisting of hydrogen, hydroxy, C.sub.1-C.sub.3hydroxyalkyl, oxo,
C.sub.2-C.sub.4acyl, C.sub.1-C.sub.3alkyl, C.sub.2-C.sub.4alkylcarboxy,
C.sub.1-C.sub.3alkoxy, and C.sub.1-C.sub.20alkanoyloxy, or may be
substituted to form a spiro five- or six-membered heterocyclic ring
containing one or two oxygen and/or sulfur heteroatoms; or any two
adjacent additional carbon ring atoms may be fused to a
C.sub.3-C.sub.8carbocyclic ring, and any one or more of the additional
nitrogen ring atoms may be substituted with substituents selected from
the group consisting of hydrogen, C.sub.1-C.sub.6alkyl,
C.sub.2-C.sub.4acyl, C.sub.2-C.sub.4hydroxyalkyl and
C.sub.3-C.sub.8alkoxyalkyl; or R.sub.1 and R.sub.2, when taken together
with the nitrogen atom to which they are directly attached in formula
(I), may form a bicyclic ring system selected from the group consisting
of 3-azabicyclo[3.2.2]nonan-3-yl, 2-azabicyclo[2.2.2]octan-2-yl,
3-azabicyclo[3.1.0]hexan-3-yl, and 3-azabicyclo[3.2.0]heptan-3-yl; and
wherein R.sub.3, R.sub.4 and R.sub.5 are independently bromine, chlorine,
fluorine, carboxy, hydrogen, hydroxy, hydroxymethyl, methanesulfonamido,
nitro, cyano, sulfamyl, trifluoromethyl, C.sub.2-C.sub.7alkanoyloxy,
C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy,
C.sub.2-C.sub.7alkoxycarbonyl, C.sub.1-C.sub.6thioalkyl, aryl or
N(R.sub.6,R.sub.7) where R.sub.6 and R.sub.7 are independently hydrogen,
acetyl, methanesulfonyl or C.sub.1-C.sub.6alkyl; or R.sub.3, R.sub.4 and
R.sub.5 are independently hydrogen, hydroxy or C.sub.1-C.sub.6alkoxy;
with the proviso that R.sub.3, R.sub.4 and R.sub.5 cannot all be
hydrogen; and wherein O-J is a leaving group. Methods of making
intermediates are also disclosed.
