A short enantioselective synthesis of N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid from geraniol.
The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.
Noe
Mark C
MC
Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA. mark.c.noe@pfizer.com
Hawkins
Joel M
JM
Snow
Sheri L
SL
Wolf-Gouveia
Lilli
L
D000080462:Acyclic Monoterpenes; D006868:Hydrolysis; D015394:Molecular Structure; D010126:Ozone / Q000737:chemistry; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry*
D000080462:Acyclic Monoterpenes; C529358:N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid; D010875:Pipecolic Acids; D013729:Terpenes; D010126:Ozone; C007836:geraniol