Methyl p-toluenesulfonate → (+/-)-alpha-(Methoxyimino)-alpha-(1-azabicyclo[3.2.1]oct-2-en-3-yl)acetonitrile

HRID 2379425Notes

Reaction equation

HRID 2379425 reaction equation
CC(C)([O-])C.[K+].[C:7]([CH:9]=[C:10]1[CH2:16][CH:15]2[CH2:17][N:12]([CH2:13][CH2:14]2)[CH2:11]1)#[N:8].[N:18]([O:20][C:21](C)(C)C)=O.C1(C)C=CC(S(OC)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[CH3:21][O:20][N:18]=[C:9]([C:10]1[CH2:16][CH:15]2[CH2:17][N:12]([CH2:13][CH2:14]2)[CH:11]=1)[C:7]#[N:8].[CH3:21][O:20][N:18]=[C:9]([C:10]1[CH2:11][N:12]2[CH2:17][CH:15]([CH:16]=1)[CH2:14][CH2:13]2)[C:7]#[N:8]

Participants

8

Reactant 5

HCID 6645Methyl p-toluenesulfonateHCID 10906Tert-Butyl nitriteHCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 53895625(+/-)3-Cyanomethylene-1-azabicyclo[3.2.1]octane

Product 2

HCID 54209096(+/-)-alpha-(Methoxyimino)-alpha-(1-azabicyclo[3.2.1]oct-2-en-3-yl)acetonitrileYield 55%HCID 54368306(+/-)-alpha-(Methoxyimino)-alpha-(1-azabicyclo[3.2.1]oct-3-en-3-yl)acetonitrileYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium tert-butoxide (0.807 g, 7.19 mmol) was added portionwise to a solution of (±)3-cyanomethylene-1-azabicyclo[3.2.1]octane (D11) (0.967 g, 6.53 mmol) in THF (40 ml) at -70° C. The resulting solution was stirred for 0.5h at -60° C., then tert-butyl nitrite (0.87 ml of approximately 90% purity, 6.58 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 1.5h. Methyl p-toluenesulphonate (1.215 g, 6.53 mmol) in THF (10 ml) was added dropwise and the resulting mixture was stirred at room temperature overnight, then poured into saturated aqueous potassium carbonate (75 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried (Na2SO4) and evaporated to a gum which was subjected to column chromatography on silica in a gradient of 1-5% methanol in chloroform to afford in order of elution (±)-α-(methoxyimino)-α-(1 -azabicyclo[3.2.1]oct-2-en-3-yl)acetonitrile (0.683 g, 55%) as a crystallising oil and (±)-α-(methoxyimino)-α-(1-azabicyclo[3.2.1]oct-3-en-3-yl)acetonitrile (0.194 g, 16%) as an oil. The latter compound was converted to the oxalate salt and recrystallised from acetone/methanol to give the title compound (E6) as a white crystalline solid m.p. 196°-198° C.

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. extractionextracted with ethyl acetate (3×100 ml)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customevaporated to a gum which

Sources & evidence

ORD record
ord-ea3f0c9ad7894074a2e871e72e74cc51
Source dataset
uspto-grants-1994_11
Patent number
US05362739

Reaction notes

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