Diisopropylamine → HCID 19823701, compound

Temperature

-12 °C

A solution of 2-[1-(3,4-dichlorophenyl)cyclobutyl]-2-dimethylaminoacetonitrile (28.3 g prepared as described in Example A(c)) in dry tetrahydrofuran (150 ml) was added with stirring to a solution of lithium diisopropylamide [prepared by the addition of a 1.6M solution of butyllithium in hexane (100 ml) to a solution of diisopropylamine (22.4 ml) in ether (200 ml) followed by removal of the solvents at 80° C. and disolution of the residue in tetrahydrofuran (100 ml)] at -20° C. The temperature of the solution was maintained at -12° C. for 30 minutes. The mixture was then cooled to -40° C. and propionaldehyde (20 ml) was added. The temperature was allowed to rise to -10° C. and an excess of aqueous ammonium chloride solution was added at the same temperature. The aqueous layer was separated and extracted with ether and the extract combined with the organic phase of the reaction mixture. The resulting organic phase was dried and the solvents removed. The residue was distilled (eliminating hydrogen cyanide) (154° C./6mm Hg to 180° C./1.2 mm Hg) to give an oil which was dissolved in petroleum ether (40°-60° C.). A solid which separated from the solution was collected by filtration and discarded and the filtrate evaporated. The residue was dissolved in methanol, oxalic acid (20 g) was added and the mixture heated at 90°-95° C. for 40 minutes. The solution was poured into water (ca. 1.5 litres) and the resulting mixture was washed with ether, basified and extracted with ether, The extract yielded an oil which was distilled in a Buchi Kugelrohr apparatus (175° C./0.9 mm Hg) to give 1-[1-(3,4-dichlorophenyl)cyclobutyl]-1-dimethylaminobutan-2-one

1. customfollowed by removal of the solvents at 80° C.
2. customat -20° C
3. temperatureThe mixture was then cooled to -40° C.
4. additionpropionaldehyde (20 ml) was added
5. customto rise to -10° C.
6. additionan excess of aqueous ammonium chloride solution was added at the same temperature
7. customThe aqueous layer was separated
8. extractionextracted with ether
9. customThe resulting organic phase was dried
10. customthe solvents removed
11. distillationThe residue was distilled (eliminating hydrogen cyanide) (154° C./6mm Hg to 180° C./1.2 mm Hg)
12. customto give an oil which
13. customA solid which separated from the solution
14. filtrationwas collected by filtration
15. customthe filtrate evaporated
16. dissolutionThe residue was dissolved in methanol
17. additionoxalic acid (20 g) was added
18. temperaturethe mixture heated at 90°-95° C. for 40 minutes
19. additionThe solution was poured into water (ca. 1.5 litres)
20. washthe resulting mixture was washed with ether
21. extractionextracted with ether
22. customThe extract yielded an oil which
23. distillationwas distilled in a Buchi Kugelrohr apparatus (175° C./0.9 mm Hg)

ORD record

ord-f30141c8c44f4c6c980d5cd873ec628b

Source dataset

uspto-grants-1991_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05047432