Water → 3-Amino-4-chloro-2-methylphenol

To a stirred solution of 3-amino-o-cresol (60 g) in anhydrous methanesulfonic acid (300 ml) was added N-chlorosuccinimide (68.3 g in five equal portions) over 2 h and 10 min, keeping the reaction temperature between 10 and 12° C. by use of a cooling bath. The dark mixture was allowed to stir overnight and warm to room temperature. It was then added to 1000 ml water with stirring (final temperature approx. 51° C.). Concentrated ammonium hydroxide (370 ml) was added with stirring, keeping the temperature between 50 and 60° C. by use of a cooling bath. The product crystallized out near the end of the addition at 50-53° C. The product slurry was cooled to ice bath temperature and held for 1 h. The product, isolated in 70.5% yield by filtration, washing with ice water, and drying in vacuo at 50° C., was 98.44% pure by area-normalized HPLC with correction for relative response factors. It contained only 0.8% of the 6-chloro isomer and 0.68% of the 4,6-dichloro impurity. Recrystallization from isopropanol-water with charcoal treatment gave, in 94% recovery, purified product that was 99.67% pure by HPLC (mp 143-144° C.).

1. custom10 min
2. customthe reaction temperature between 10 and 12° C.
3. stirringwith stirring (final temperature approx. 51° C.)
4. stirringwith stirring
5. customthe temperature between 50 and 60° C.
6. customThe product crystallized out near the end of the addition at 50-53° C
7. temperatureThe product slurry was cooled to ice bath temperature
8. waitheld for 1 h
9. customThe product, isolated in 70.5% yield by filtration
10. washwashing with ice water
11. customdrying in vacuo at 50° C.
12. customRecrystallization from isopropanol-water with charcoal treatment
13. customgave, in 94% recovery
14. custompurified product that

ORD record

ord-11160bd35dbd4a038309e7cab71c878d

Source dataset

uspto-grants-1999_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05952362