Formic Acid → 1-(4-Chlorophenyl)ethylamine

Temperature

180 °C

A mixture of 4'-chloroacetophenone (103.3 g), formamide (98%; 123 g) and formic acid (97%; 8.3 ml) was stirred and heated at 180° C. The water produced in the reaction was removed by distillation together with some of the starting acetophenone which was separated and returned to the reaction vessel. Formic acid (70 ml total) was added in small aliquots over 8 hours. The reaction mixture was cooled and exhaustively extracted with toluene. The combined toluene extracts were washed with water, dried, filtered and the filtrate evaporated. Concentrated hydrochloric acid (70 ml) was added to the residue and the mixture boiled under reflux for 1 hour. The mixture was cooled, extracted with toluene and the aqueous layer basified with aqueous sodium hydroxide (5M). The solution was steam distilled until 1.4 1 of distillate had been collected and the distillate was extracted with ethyl acetate. The combined ethyl acetate extracts were dried, filtered and the filtrate evaporated to give an oil which was distilled to give (±)-1-(4-chlorophenyl)ethylamine, b.p. 120°-122° C. (19 mmHg). A small portion of the distillate was dissolved in dry ether and an equal volume of saturated ethereal hydrogen chloride was added. The solid formed was collected by filtration and dried to give (±)-1-(4-chlorophenyl)ethylamine hydrochloride, m.p. 186°-189° C.

1. customwas removed by distillation together with some of the starting acetophenone which
2. customwas separated
3. additionFormic acid (70 ml total) was added in small aliquots over 8 hours
4. temperatureThe reaction mixture was cooled
5. extractionexhaustively extracted with toluene
6. washThe combined toluene extracts were washed with water
7. customdried
8. filtrationfiltered
9. customthe filtrate evaporated
10. additionConcentrated hydrochloric acid (70 ml) was added to the residue
11. temperatureunder reflux for 1 hour
12. temperatureThe mixture was cooled
13. extractionextracted with toluene
14. distillationdistilled until 1.4 1 of distillate
15. customhad been collected
16. extractionthe distillate was extracted with ethyl acetate
17. dry with materialThe combined ethyl acetate extracts were dried
18. filtrationfiltered
19. customthe filtrate evaporated
20. customto give an oil which
21. distillationwas distilled

ORD record

ord-865a39afe39f40f1a4d6b6e40ba3df68

Source dataset

uspto-grants-1996_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05547972