title: A short enantioselective synthesis of N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid from geraniol.
abstract: 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.
authors.affiliation: Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA. mark.c.noe@pfizer.com
authors.forename: Mark C
authors.initials: MC
authors.lastname: Noe
authors.forename: Joel M
authors.initials: JM
authors.lastname: Hawkins
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Snow
authors.forename: Lilli
authors.initials: L
authors.lastname: Wolf-Gouveia
mesh_terms: 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*
chemical_list: D000080462:Acyclic Monoterpenes; C529358:N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid; D010875:Pipecolic Acids; D013729:Terpenes; D010126:Ozone; C007836:geraniol