Hydrogen Cyanide → HCID 19823811, compound

Temperature

3 °C

A solution of 2-[1-(3,4-dichlorophenyl)cyclobutyl]-2-dimethylaminoacetonitrile (11.3 g prepared as described in Example A(c)) in tetrahydrofuran (20 ml) was added over a period of ten minutes to a solution of lithium diisopropylamide at -50° C. [prepared by the addition of a 2.7M solution of butyllithium in hexane (24.7 ml) to a solution of diisopropylamine (10.25 ml) in dry tetrahydrofuran (30 ml) at 10°-15° C. under argon] and the mixture was allowed to warm to 3° C. and maintained at 3° C. for 30 minutes. The mixture was cooled to -70° C. and cyclohexanecarbaldehyde (11.5 g) was added with stirring over a period of 20 minutes. Stirring was continued at this temperature for a further 40 minutes and then saturated aqueous ammonium chloride solution (100 ml) was added slowly at -70° C. The mixture was allowed to warm to 20°-25° C. and the aqueous layer was separated and extracted with ether. The ether extracts were combined with the organic layer of the reaction mixture, dried and evaporated to give an oil which was heated (eliminating hydrogen cyanide) at 90°-95° C. for 3 hours and then cooled and dissolved in methanol (100 ml). Oxalic acid (10 g) was added and the mixture heated at 90°-95° C. for one hour. The mixture was cooled, basified and extracted with ether. The ether extract was dried and evaporated to give an oil which was purified by flash chromatography using a 95:5 mixture of petroleum ether and ether as eluant. The resulting oil solidified on standing and was recrystallised from petroleum ether (b.p. 60°-80° C.) to give 1-cyclohexyl-2-[1-(3,4-dichlorophenyl)cyclobutyl]-2-dimethylaminoethanone (m.p. 79°-80° C.).

1. temperaturemaintained at 3° C. for 30 minutes
2. temperatureThe mixture was cooled to -70° C.
3. stirringStirring
4. waitwas continued at this temperature for a further 40 minutes
5. temperatureto warm to 20°-25° C.
6. customthe aqueous layer was separated
7. extractionextracted with ether
8. customdried
9. customevaporated
10. customto give an oil which
11. temperaturecooled
12. temperaturethe mixture heated at 90°-95° C. for one hour
13. temperatureThe mixture was cooled
14. extractionextracted with ether
15. extractionThe ether extract
16. customwas dried
17. customevaporated
18. customto give an oil which
19. customwas purified by flash chromatography
20. additiona 95:5 mixture of petroleum ether and ether as eluant
21. customwas recrystallised from petroleum ether (b.p. 60°-80° C.)

ORD record

ord-0d61f97515c34fa0ab8d2f78ceec5b05

Source dataset

uspto-grants-1991_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05047432