Hydrochloric Acid → HCID 12039994, compound

A mixture of 2-methanesulfonyloxy anisole (240 g) and 3-methylcrotonic acid (39 g) was stirred, and to the thus mixed solution, aluminum chloride (104 g) was added, and the mixture was stirred for 5 hours at 70° C., and then further stirred for 2 hours at 100° C. The obtained solution was cooled to about room temperature, and then 6N hydrochloric acid (HCl) solution (390 ml) was added thereto, and the mixture was stirred for 3 hours vigorously. The solution obtained was extracted with the use of methylene chloride (300 ml), and the organic layer separated was further extracted with the use of two normal (2N) sodium hydroxide (NaOH) aqueous solution (400 ml). Subsequently, 6N hydrochloric acid (HCl) solution was further added to the aqueous layer separated, to acidify, the solution. The obtained aqueous solution was extracted with methylene chloride (300 ml) twice, and thereafter, thus obtained organic layer was concentrated under reduced pressure to obtain a residue. Subsequently, to the residue thus obtained, 6N NaOH aqueous solution (300 ml) was added, and the mixture was stirred for 4 hours at 100° C. for mixing. The obtained reaction solution was cooled to a room temperature, and then 6N HCl solution was added thereto, to acidify the solution. The obtained solution was extracted with ethyl acetate. From the organic solution separated, the solvent therein was removed by distillation under reduced pressure, and thereafter, the obtained crude crystals were recrystallized with toluene to obtain 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyric acid as objective (33.2 g; yield: 37.9% to the 3-methylcrotonic acid).

1. stirringthe mixture was stirred for 5 hours at 70° C.
2. stirringfurther stirred for 2 hours at 100° C
3. temperatureThe obtained solution was cooled to about room temperature
4. stirringthe mixture was stirred for 3 hours vigorously
5. customThe solution obtained
6. extractionwas extracted with the use of methylene chloride (300 ml)
7. customthe organic layer separated
8. extractionwas further extracted with the use of two normal (2N) sodium hydroxide (NaOH) aqueous solution (400 ml)
9. additionSubsequently, 6N hydrochloric acid (HCl) solution was further added to the aqueous layer
10. customseparated
11. extractionThe obtained aqueous solution was extracted with methylene chloride (300 ml) twice
12. concentrationthus obtained organic layer was concentrated under reduced pressure
13. customto obtain a residue
14. customSubsequently, to the residue thus obtained
15. stirringthe mixture was stirred for 4 hours at 100° C.
16. additionfor mixing
17. customThe obtained reaction solution
18. extractionThe obtained solution was extracted with ethyl acetate
19. customFrom the organic solution separated
20. customthe solvent therein was removed by distillation under reduced pressure
21. customthe obtained crude crystals
22. customwere recrystallized with toluene

ORD record

ord-3bd9c16f568d4ebaaf1b64600e496c55

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06693214B2