Substituted 8-azabicyclo[3.2.1]octan-3-ol compounds disclosed in U.S. Pat. No. 6,262,066 are NOP receptor agonists (previously known as ORL-1 receptor agonists) useful in the treatment of various disorders such as pain, anxiety and cough. U.S. Pat. No. 6,262,066 discloses a process for preparing the claimed compounds comprising an expensive and unstable tropinone as a starting material.
A preferred group of 8-azabicyclo[3.2.1]octan-3-ols, including 8-[bis(2-chlorophenyl)methyl]-3-pyrimidin-2-yl-8-azabicyclo[3.2.1]octan-3-ol, is specifically disclosed in U.S. Pat. No. 6,727,254. The multi-step process disclosed in U.S. Pat. No. 6,727,254 comprises reaction of a tropinone with a diphenylmethyl derivative, followed by reaction with a tributyltin derivative of pyrimidine and an alkyl lithium derivative.