Hydrochloric Acid → HCID 12112198, compound

Temperature

70 °C

To hydroxy(1-acetyl-4,6-dimethylindolin-5-yl)acetic acid (3.0 g) obtained in Example 1 and 7.5% palladium on charcoal (1.3 g, wet (water content: 53.1%)) placed in a 100-ml autoclave was added a saturated solution of hydrogen chloride in ethanol (30 ml). After degassing with nitrogen for 3 times (5 kg/cm2 for each) and replacing nitrogen with hydrogen for 3 times (5 kg/cm2 for each) successively, the resulting mixture was stirred for 5 hours at 70° C. under a pressurized hydrogen atmosphere (5 kg/cm2). The reaction mixture was filtered to remove palladium on charcoal, which was washed with ethanol (45 ml). The filtrate and washing were combined and concentrated in vacuo, and after adding acetone (30 ml) to the residue, the resulting mixture was concentrated in vacuo once again. Subsequently, to the residue obtained were added acetone (30 ml), diisopropylethylamine (4.4 g, 3.0 equivalent) and acetyl chloride (0.81 ml, 1.0 equivalent) successively, and the resulting mixture was refluxed for 10 minutes. The reaction mixture was concentrated in vacuo. To the residue obtained were added water (30 ml) and ethyl acetate (60 ml) successively, and after stirring, the resulting mixture was filtered to remove insoluble precipitates, which were washed with water (30 ml) and ethyl acetate (30 ml) successively. The filtrate and washing were combined, and both organic and aqueous layers were separated by partitioning. The separated aqueous layer was extracted with ethyl acetate (30 ml) once again, and the extract was combined with the organic layer separated above. The organic layer was washed with water (30 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford the title compound (2.86 g, yield: 91%) as colourless crystals.

1. customAfter degassing with nitrogen for 3 times (5 kg/cm2 for each) and
2. filtrationThe reaction mixture was filtered
3. customto remove palladium on charcoal, which
4. washwas washed with ethanol (45 ml)
5. washThe filtrate and washing
6. concentrationconcentrated in vacuo
7. additionafter adding acetone (30 ml) to the residue
8. concentrationthe resulting mixture was concentrated in vacuo once again
9. customSubsequently, to the residue obtained
10. temperaturethe resulting mixture was refluxed for 10 minutes
11. concentrationThe reaction mixture was concentrated in vacuo
12. customTo the residue obtained
13. stirringafter stirring
14. filtrationthe resulting mixture was filtered
15. customto remove insoluble precipitates, which
16. washwere washed with water (30 ml) and ethyl acetate (30 ml) successively
17. washThe filtrate and washing
18. customboth organic and aqueous layers were separated
19. customby partitioning
20. extractionThe separated aqueous layer was extracted with ethyl acetate (30 ml) once again
21. customseparated above
22. washThe organic layer was washed with water (30 ml)
23. dry with materialdried over anhydrous magnesium sulfate
24. concentrationconcentrated under reduced pressure

ORD record

ord-0bc8b62a4d14491aaef1773d88c88ec9

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07012147B2