| 摘要 |
The present invention relates to a process for preparing substituted 8-azabicyclo[3.2.1]octan-3-ols having the structural formula I or a pharmaceutically acceptable salt or solvate thereof, wherein R is benzyl, R5-benzyl, allyl, -C(O)R6, -C(O)OR8 or -CH(R7)2; R1 is optionally substituted aryl or optionally substituted heteroaryl; and R5, R6, R7 and R8 are as defined in the specification; comprising a) reacting an amine of formula II <?in-line-formulae description="In-line Formulae" end="lead"?>R-NH2 II<?in-line-formulae description="In-line Formulae" end="tail"?> with 2,5-dimethoxytetrahydrofuran or HC(O)(CH2)2C(O)H, and C(O)(CH2C(O)OR4)2, wherein R4 is H or alkyl, to obtain a compound of formula III b) reacting a compound of formula III with I-R1, alkyl lithium, and optionally a lithium salt, to obtain a compound of formula I; and c) optionally converting a compound of formula I wherein R is benzyl, R5-benzyl, allyl, -C(O)R6 or -C(O)OR8 to a compound of formula I wherein R is -CH(R7)2. Intermediates in the process are also claimed. |
