Hydrochloric Acid → (R)-3-hydroxytetradecanoic acid

Typically, hydrogenation of β-ketoester XVI, e.g., methyl 3-oxotetradecanoate, is conducted in a conventional hydrogenation solvent including an alkyl alcohol, such as ethanol or preferably in methanol, at a reaction temperature of about 80° C. The concentration of the substrate (i.e., β-ketoester XVI) in hydrogenation reaction is generally at about 40 wt %, and the ratio of HCl to Ru(OAc)2((R)-MeOBIPHEP) in the hydrogenation catalyst is about 20:1. A typical ratio of methyl 3-oxotetradecanoate to the hydrogenation catalyst is about 50,000:1. To this reaction mixture, typically about 40 bar of technical grade hydrogen gas is added, and the reaction is allowed to proceed for about 4 hours (h). The resulting methyl (R)-3-hydroxy tetradecanoate is then saponified by diluting the crude hydrogenation solution in methanol and 28% aqueous sodium hydroxide solution at room temperature. The saponified product is then acidified with an acid, such as sulfuric acid, to isolate (R)-3-hydroxy tetradecanoic acid. In this manner, the β-hydroxy acid IIA, such as(R)-3-hydroxy tetradecanoic acid, can be produced in at least about 90% isolated yield from the corresponding β-ketoester XVI, more preferably in at least about 93% isolated yield and most preferably in at least about 95% isolated yield. The enantiomeric excess of the product is at least about 90%ee, preferably at least about 95%ee, and more preferably at least about 99%ee. The enantiomeric excess can be increased to at least about 95%ee after a single recrystallization, preferably at least about 99%ee, and most preferably at least about 99.5%ee.

1. customat a reaction temperature of about 80° C
2. customat room temperature

ORD record

ord-32c7cb6714ce48699ca6e954c64190c1

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06552204B1