Hydrochloric Acid → Pentanenitrile, 4,4-dimethyl-3-oxo-

Temperature

-70 °C

Cyanoacetic acid (8.5 g) was dissolved in dry THF (300 ml), placed under an inert atmosphere and the solution cooled using a dry ice-acetone bath. Butyllithium (80 ml of a 2.5M solution in hexane) was added dropwise over 1 hour. During the addition the internal reaction temperature was maintained below -65° C. The reaction mixture was stirred in the dry ice-acetone bath for 1 hour and then the bath was removed and the reaction stirred for an additional hour, during which time the internal temperature rose to -45° C. The resultant reaction mixture was cooled to -70° C. and trimethylacetyl chloride (6.0 g) in THF (50 ml) added dropwise over 30 minutes while keeping the temperature of the reaction mixture below -65° C. The reaction mixture was allowed to stir in a dry ice-acetone bath for 1 hour and then allowed to warm to room temperature overnight. The resultant mixture was acidified by the addition of 2N HCl (200 ml) and diluted with CH2Cl2 (500 ml). The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (MgSO4) and, after removal of the drying agent by filtration, the solvents were removed. The residue was dissolved in ether (200 ml) and the etheral solution extracted with 2N NaOH (twice with 50 ml portions). To the combined aqueous extracts was added conc. HCl to adjust the solution to pH 1. The resulting mixture was extracted with ether. The combined extracts were dried (MgSO4) and, after removal of the drying agent by filtration, the solvents were removed to afford 5.6 g of 4,4-dimethyl-3-oxopentanonitrile as an orange oil which slowly solidified; m.p. 60° C.

1. temperaturethe solution cooled
2. additionDuring the addition the internal reaction temperature
3. temperaturewas maintained below -65° C
4. customthe bath was removed
5. customrose to -45° C
6. customThe resultant reaction mixture
7. customthe temperature of the reaction mixture below -65° C
8. stirringto stir in a dry ice-acetone bath for 1 hour
9. temperatureto warm to room temperature overnight
10. customThe layers were separated
11. extractionthe aqueous layer was extracted with CH2Cl2
12. dry with materialThe combined organic layers were dried (MgSO4)
13. customafter removal of the drying agent
14. filtrationby filtration
15. customthe solvents were removed
16. dissolutionThe residue was dissolved in ether (200 ml)
17. extractionthe etheral solution extracted with 2N NaOH (twice with 50 ml portions)
18. additionTo the combined aqueous extracts was added conc. HCl
19. extractionThe resulting mixture was extracted with ether
20. dry with materialThe combined extracts were dried (MgSO4)
21. customafter removal of the drying agent
22. filtrationby filtration
23. customthe solvents were removed

ORD record

ord-6e36b8eefe4f44598d1a659ca3edd22a

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05804532