Carbon tetrabromide → Methyl 8-bromooctanoate

Temperature

4 °C

Cis-9,10-octadecenoamide, cis-11,12-octadecenoamide, and trans-9,10-octadecenoamide were prepared from their respective acids as follows: cis-9,10-octadecenoic acid (oleic acid) in CH2Cl2 (0.2M) at 0° C. was treated with oxalyl chloride (3 eq) and stirred at 25° for 4 hour. Removal of solvent followed by treatment with saturated aqueous NH4OH at 0° C. gave cis-9,10-octadecenoamide, which was purified by silica gel column chromatography (40-75% ethyl acetate-hexanes gradient elution). Cis-8,9-octadecenoamide was synthesized as follows: 1) Suberic acid monomethyl ester in THF at -20° C. was treated with BH3 -THF (1.05 eq) and stirred for 12 hour at 25° C. to afford methyl 8-hydroxyoctanoate (18); 2) Methyl 8-hydroxyoctanoate in CH2Cl2 at 0° C. was treated sequentially with CBr4 (1.3 eq) and Ph3P (1.4 eq) and stirred for 10 hour at 4° C. to give methyl 8-bromooctanoate; 3) Methyl 8-bromooctanoate was dissolved in CH3CN (0.8M) and warmed at reflux. Ph3P (1.1 eq) was added to the solution and stirring was continued for 20 hour to afford the corresponding phosphonium salt; 4) The phosphonium salt of methyl 8-bromooctanoate was dissolved in THF at 25° C. and treated with KHMDS (1.1 eq). After stirring at reflux for 1 hour, the solution was cooled to -78° C. and decanal (1.5 eq) was added. The mixture was allowed to warm to 25° C. and stirred for 30 minute to afford methyl cis-8,9-octadecenoate; 5) Methyl cis-8,9-octadecenoate was hydrolyzed to afford cis-8,9-octadecenoic acid with LiOH (3 eq) in THF-CH3OH--H2O (3:1:1); 6) Conversion of cis-8,9-octadecenoic acid to cis-8,9-octadecenoamide was conducted as described above.

ORD record

ord-a21fe5de61bf41b7ab31a6aa20b2c26a

Source dataset

uspto-grants-1997_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05612380