p-Toluidine → Benzenamine, 4-methyl-, hydrochloride (1:1)

In a 500 ml 3-neck flask with nitrogen purge, drying tube and stirrer is added 250 ml of dry pyridine. To this is added 10 g (0.0477 mole) of 1-acetyl-6-chloro-indol-3-ol. The flask is cooled to less than about 10° C. in a methanol/dry ice bath in a darkened hood. To the suspension is added 5.5 ml of phosphorous oxychloride. The temperature is allowed to come up to 0° C. and maintained for 4 hours. The reaction mixture turns a light red color. The reaction mixture is allowed to stir overnight. The solution is rotovaped to dryness (less than about 50° C.) using a cold trap and vacuum pump. The resulting residue is taken up in 100 ml of ice cold water and adjusted to pH of 9.0 with 10% KOH. The dark solution is rotovaped to dryness and traces of water removed by 3 evaporations of 100 ml portions of ethanol. The resulting solid residue is dissolved in 100 ml of dry methanol. To this dark solution is added a 20 ml portion of dry methanol containing 1.6 g of potassium metal. This mixture is stirred overnight on a stirring plate. The mixture is neutralized with a small portion of acetic acid to a pH between 5.5 and 6.0. This solution is rotovaped to dryness. The residue is dissolved in 100 ml of water and charcoal filtered. A solution of 6.9 g of p-toluidine hydrochloride is prepared in 100 ml of water. The p-toluidine solution is stirred into the reaction solution. The resulting precipitate is collected by vacuum filtration, washed with ethanol and vacuum dried.

1. customIn a 500 ml 3-neck flask with nitrogen purge
2. customdrying tube and stirrer
3. additionis added 250 ml of dry pyridine
4. temperatureThe flask is cooled to less than about 10° C. in a methanol/dry ice bath in a darkened hood
5. customto come up to 0° C.
6. temperaturemaintained for 4 hours
7. customis rotovaped to dryness (less than about 50° C.)
8. customremoved by 3 evaporations of 100 ml portions of ethanol
9. dissolutionThe resulting solid residue is dissolved in 100 ml of dry methanol
10. additionTo this dark solution is added a 20 ml portion of dry methanol containing 1.6 g of potassium metal
11. stirringThis mixture is stirred overnight on a stirring plate
12. dissolutionThe residue is dissolved in 100 ml of water
13. filtrationcharcoal filtered
14. filtrationThe resulting precipitate is collected by vacuum filtration
15. washwashed with ethanol and vacuum
16. customdried

ORD record

ord-a7169e8bd68d4067a410301c65c08f2e

Source dataset

uspto-grants-1994_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05364767