Sulfuric Acid → HCID 67545269, compound

HRID 2176085Notes

Reaction equation

HRID 2176085 reaction equation
Cl.[C:2]1([CH3:10])[CH:7]=[CH:6][C:5]([NH:8]N)=[CH:4][CH:3]=1.O=[C:12]1[CH2:18][CH:17]2[N:19](C(OC(C)(C)C)=O)[CH:14]([CH2:15][CH2:16]2)[CH2:13]1.S(=O)(=O)(O)O>O1CCOCC1>[CH3:10][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[NH:8][C:12]1[CH2:13][CH:14]3[NH:19][CH:17]([C:18]2=1)[CH2:16][CH2:15]3

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 125044-Methylphenylhydrazine monohydrochlorideHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylate

Product 1

HCID 67545269HCID 67545269, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

4-Tolylhydrazine hydrochloride (1.90 g, 12.0 mmol) and tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate (2.70 g, 12.0 mmol; Fluka) were heated at 50° C. in anhydrous dioxane (80 mL) for one hour. Sulfuric acid (3.2 mL) was added dropwise, and the resulting mixture was heated at 80° C. overnight. After cooling the mixture to room temperature, the dioxane phase was decanted. The remaining residue was dissolved in methanol (12 mL) and added slowly to a stirred solution of concentrated ammonium hydroxide (30 mL) kept at room temperature with a water bath. The resulting mixture was extracted with ethyl acetate (3×), and the combined organic phases were washed with brine, dried (sodium sulfate), concentrated, and purified by chromatography (silica gel, 0-5% gradient of concentrated aqueous ammonium hydroxide in acetonitrile) to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.59-1.72 (m, 1H), 1.93-2.25 (m, 3H), 2.54 (d, J=16, 1H), 3.25 (dd, J=16, 4.7, 1H), 3.91-3.99 (m, 1H), 4.49 (d, J=4.8, 1H), 6.83 (d, J=8.2, 1H), 7.12 (d, J=8.2, 1H), 7.19 (s, 1H); MS (ESI) m/z 213 (M+H)+.

Workup

  1. temperatureAfter cooling the mixture to room temperature
  2. customthe dioxane phase was decanted
  3. dissolutionThe remaining residue was dissolved in methanol (12 mL)
  4. additionadded slowly to a stirred solution of concentrated ammonium hydroxide (30 mL)
  5. customkept at room temperature with a water bath
  6. extractionThe resulting mixture was extracted with ethyl acetate (3×)
  7. washthe combined organic phases were washed with brine
  8. dry with materialdried (sodium sulfate)
  9. concentrationconcentrated
  10. custompurified by chromatography (silica gel, 0-5% gradient of concentrated aqueous ammonium hydroxide in acetonitrile)

Sources & evidence

ORD record
ord-e4b665d0690a4bdaacb485f868b3f2dd
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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