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

ORD record

ord-4d29c4917d134e7ab83a742aa01d725d

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06057349