Acetonitrile → 1-Cyano-2-(cyanomethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalene

Temperature

-78 °C

To a solution of 1.05 mL (7.5 mmol) of diisopropylamine in 10 mL of THF at -78° C., under a nitrogen atmosphere, was added n-butyllithium (2.2 mL of a 2.5M solution in THF, 5.5 mmol) and the resultant solution was stirred at -78° C. for 40 min. To the stirred solution was added, dropwise over a 25 minute period, a solution of 274 μL (5.25 mmol) of acetonitrile in 5 mL of THF. The solution was stirred for 20 min at -78° C. and then a solution of 926 mg (5 mmol) of 1-cyano-6-methoxy-3,4-dihydronaphthalene (the product of Step 2 of Example 1) in 5 mL of THF was added via syringe pump over a 20 min period. The reaction mixture then allowed to warm to ambient temperature and was stirred at ambient temperature for 1 h and then the reaction was quenched by pouring the reaction mixture into and then the reaction was quenched by pouring the reaction mixture into saturated aqueous ammonium chloride solution. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluted with 25% ethyl acetate in hexane to give 840 mg (74% yield) of the title compound as a 1:1 mixture of the cis and trans isomers; MS DCl--NH3M/Z: 244 (M+H)+.

1. additionTo the stirred solution was added, dropwise over a 25 minute period
2. stirringThe solution was stirred for 20 min at -78° C.
3. temperatureto warm to ambient temperature
4. stirringwas stirred at ambient temperature for 1 h
5. customthe reaction was quenched
6. additionby pouring the reaction mixture into and then the reaction
7. customwas quenched
8. additionby pouring the reaction mixture into saturated aqueous ammonium chloride solution
9. customThe layers were separated
10. extractionthe aqueous layer was extracted with ethyl acetate
11. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe residue was purified by chromatography on silica gel
15. washeluted with 25% ethyl acetate in hexane

ORD record

ord-2381c22df2194b6c83a6f440b9b07972

Source dataset

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05248677