Hydrochloric Acid → HCID 19955532, compound

Temperature

-78 °C

Under a nitrogen atmosphere, a stirred solution of 2.3 mL (0.044 mole) of acetonitrile in 50 mL of tetrahydrofuran was cooled to about -80° C., and 17.7 mL (0.044 mole) of n-butyllithium (2.5M in hexanes) was added dropwise at a rate to maintain the reaction mixture temperature below -75° C. Upon completion of addition, the reaction mixture was stirred at -78° C. for 30 minutes. After this time a solution of 10.3 grams (0.040 mole) of ethyl 3-(3-phenylphenyl)propanoate in 100 mL of tetrahydrofuran was added dropwise at a rate to maintain the reaction mixture temperature below -75° C. Upon completion of addition, the reaction mixture was stirred at -78° C. for one hour. After this time the reaction mixture was allowed to warm to ambient temperature, then was cooled to about 0° C., and 30 mL of aqueous 6N hydrochloric acid was added dropwise. Upon completion of addition, the reaction mixture was allowed to Warm to ambient temperature where it was stirred for 30 minutes. The mixture was poured into 200 mL of water, and then it was extracted with two 100 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. NMR analysis of the residual oil indicated that it was impure. The oil was dissolved in 10:1 methylene chloride and acetone, and the solution was passed through a column of basic alumina that was deactivated to Level III with water. The eluate was concentrated under reduced pressure, yielding 5.9 grams of 3-oxo-5-(3-phenylphenyl)pentanenitrile. The NMR spectrum was consistent with the proposed structure.

1. temperatureto maintain the reaction mixture temperature below -75° C
2. additionUpon completion of addition
3. temperatureto maintain the reaction mixture temperature below -75° C
4. additionUpon completion of addition
5. stirringthe reaction mixture was stirred at -78° C. for one hour
6. temperatureto warm to ambient temperature
7. temperaturewas cooled to about 0° C.
8. additionUpon completion of addition
9. temperatureto Warm to ambient temperature where it
10. stirringwas stirred for 30 minutes
11. extractionit was extracted with two 100 mL portions of diethyl ether
12. dry with materialThe combined extracts were dried with magnesium sulfate
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under reduced pressure to a residual oil
15. dissolutionThe oil was dissolved in 10:1 methylene chloride and acetone
16. concentrationThe eluate was concentrated under reduced pressure

ORD record

ord-07696342cde0449d8457d0a778829b47

Source dataset

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05627189