Methane → HCID 19108688, compound

A mixture of 6-chloro-m-anisidine hydrochloride (21.48 g, 0.11 mole), triethylamine (15.2 ml, 0.11 mole) and 150 ml trimethyl orthoformate was heated at reflux for 3.5 hours. To the mixture was added 150 ml of toluene and some charcoal. After stirring, the mixture was filtered and the filtrate was evaporated to an oil. The oil was redissolved in 150 ml of methanol and reacted with aminoacetaldehyde dimethyl acetal (12 ml, 0.11 mole) at reflux for four hours. The reaction was concentrated and the residue was dissolved in toluene. The toluene solution was extracted twice (total volume 100 ml) with 2N hydrochloric acid solution. The extracts were combined, heated at reflux temperature for five hours, and then concentrated. The residue was dissolved in water and neutralized first with 50% sodium hydroxide and finished up with sodium bicarbonate solution. Some oily material deposited and crystallized upon addition of toluene. The mixture was filtered, the layers of the filtrate were separated, and the aqueous layer extracted three times with toluene-acetonitrile. The organic layers were combined, dried over sodium sulfate, and concentrated to a dark brown oil (15 g). TLC (silica gel eluted with 10% methanol in methylene chloride) of this oil showed mainly two spots at Rf 0.8 and 0.2. The oil was chromatographed on 150 g of silica gel and eluted with 10% methanol in methylene chloride.

1. temperaturewas heated
2. temperatureat reflux for 3.5 hours
3. filtrationthe mixture was filtered
4. customthe filtrate was evaporated to an oil
5. dissolutionThe oil was redissolved in 150 ml of methanol
6. temperatureat reflux for four hours
7. concentrationThe reaction was concentrated
8. dissolutionthe residue was dissolved in toluene
9. extractionThe toluene solution was extracted twice (total volume 100 ml) with 2N hydrochloric acid solution
10. temperatureheated
11. temperatureat reflux temperature for five hours
12. concentrationconcentrated
13. dissolutionThe residue was dissolved in water and neutralized first with 50% sodium hydroxide
14. customcrystallized upon addition of toluene
15. filtrationThe mixture was filtered
16. customthe layers of the filtrate were separated
17. extractionthe aqueous layer extracted three times with toluene-acetonitrile
18. dry with materialdried over sodium sulfate
19. concentrationconcentrated to a dark brown oil (15 g)
20. washTLC (silica gel eluted with 10% methanol in methylene chloride) of this oil
21. customThe oil was chromatographed on 150 g of silica gel
22. washeluted with 10% methanol in methylene chloride

ORD record

ord-b7e1657d73a6421ab560135c91430929

Source dataset

uspto-grants-1993_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05273993