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

HRID 1646591

Reaction equation

HRID 1646591 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13](#[N:15])[CH3:14].[C:16]([C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[CH2:21][CH2:20][CH:19]=1)#[N:17]>C1COCC1>[C:13]([CH:14]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[CH2:21][CH2:20][CH:19]1[CH2:18][C:16]#[N:17])#[N:15]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 30144661-Naphthalenecarbonitrile, 3,4-dihydro-6-methoxy-HCID 178418339Butyllithium

Product 1

HCID 197932931-Cyano-2-(cyanomethyl)-6-methoxy-1,2,3,4-tetrahydronaphthaleneYield 74.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-78 °C

Procedure

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 2.5 M 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 was stirred at ambient temperature for 1 h 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 DCI-NH3M/Z: 244 (M+H)+.

Workup

  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 was stirred at ambient temperature for 1 h
  5. customthe reaction was quenched
  6. additionby pouring the reaction mixture into saturated aqueous ammonium chloride solution
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by chromatography on silica gel
  13. washeluted with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a8dc4796b12a4b409d33a58be40701b4
Source dataset
uspto-grants-1993_01
Patent number
US05180733

Linked notes

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