Hydrochloric Acid → Methyl 9-oxo-hexadecanoate

Temperature

60 °C

Under a nitrogen atmosphere, monomethyl azelate (6.70 g, 33.1 mmol), commercially available from Tokyo Chemical Industry Co., Ltd., was dissolved in toluene (60 mL), N,N-dimethylformamide (DMF, 25.6 μL, 0.331 mmol) was added thereto, and the solution was warmed to 60° C. While maintaining the temperature at 60° C., a solution of oxalyl chloride (2.94 mL, 34.8 mmol) in toluene (7.0 mL) was added dropwise over 10 minutes. After completion of the dropwise addition, the mixture was stirred at 60° C. for 2.0 hours. Toluene and oxalyl chloride were distilled off under reduced pressure, and subsequently tetrahydrofuran (THF, 67 mL) was added to distill off the solvent. Under a nitrogen atmosphere, this crude product was dissolved in THF (50 mL), tris(2,4-pentadionato) iron (III) (Fe(acac)3, 0.585 g, 0.166 mmol) was added thereto, and the solution was cooled to −40° C. Subsequently, a dilution of n-heptyl magnesium bromide (1 M solution in THF, 36.4 mL, 36.4 mmol) with THF (30 mL) was added dropwise over 1 hour. After completion of the dropwise addition, the mixture was stirred at −40° C. for 1.5 hours. To the reaction solution was added 0.5 M aqueous hydrochloric acid solution (40 mL) to stop the reaction, and the solution was extracted with ethyl acetate. The aqueous layer was washed with ethyl acetate, and the organic layers were combined, washed sequentially with water, a saturated sodium bicarbonate aqueous solution, and a saturated brine and dried over anhydrous sodium sulfate. After the organic layer was filtered and the solvent was distilled off, the resulting residue was purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.2) to obtain methyl 9-oxo-hexadecanoate (No. 4984860; 7.33 g, 78% yield).

1. temperatureWhile maintaining the temperature at 60° C.
2. additionAfter completion of the dropwise addition
3. distillationToluene and oxalyl chloride were distilled off under reduced pressure, and subsequently tetrahydrofuran (THF, 67 mL)
4. additionwas added
5. distillationto distill off the solvent
6. dissolutionUnder a nitrogen atmosphere, this crude product was dissolved in THF (50 mL)
7. temperaturethe solution was cooled to −40° C
8. additionAfter completion of the dropwise addition
9. stirringthe mixture was stirred at −40° C. for 1.5 hours
10. customthe reaction
11. extractionthe solution was extracted with ethyl acetate
12. washThe aqueous layer was washed with ethyl acetate
13. washwashed sequentially with water
14. dry with materiala saturated sodium bicarbonate aqueous solution, and a saturated brine and dried over anhydrous sodium sulfate
15. filtrationAfter the organic layer was filtered
16. distillationthe solvent was distilled off
17. customthe resulting residue was purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.2)

ORD record

ord-e84671805bb7491481a4ba7e7d71316c

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266853B2