Hydrochloric Acid → 5-((4-Bromo-2-formylphenyl)(isobutyl)amino)pentanoic acid

Temperature

110 °C

A mixture of 1-isobutyl-2-piperidone (8.8 g) and aqueous methanesulfonic acid solution (10.9 g/19 ml) was refluxed at 110° C. for 3 days. To the mixture which was previously cooled to room temperature, were added water (10 ml) and sodium carbonate (18.0 g) slowly. Then, after heating the mixture at 50° C. for 1 hour, DMSO (13 ml) was added. The resulting mixture was heated to 135° C., and then a solution of 5-bromo-2-fluorobenzaldehyde (11.5 g) in DMSO (15 ml) was added dropwise. After stirring at 135° C. for 6 hours, the mixture was cooled to 0° C., and the mixture was adjusted to pH 2.5 by using 6N hydrochloric acid. After ethyl acetate extraction, the organic layer was dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate) to obtain brown oil of 5-(4-bromo-2-formyl-N-isobutylanilino)pentanoic acid (15.3 g).

1. temperatureTo the mixture which was previously cooled to room temperature
2. temperatureThen, after heating the mixture at 50° C. for 1 hour
3. temperatureThe resulting mixture was heated to 135° C.
4. temperaturethe mixture was cooled to 0° C.
5. extractionAfter ethyl acetate extraction
6. dry with materialthe organic layer was dried over magnesium sulfate
7. distillationThe solvent was distilled off under reduced pressure
8. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate)

ORD record

ord-fc27a9d38a3546e7b7ef75c048989ecc

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741943B2