Nitric Acid → HCID 178526628, compound

HRID 724096Notes

Reaction equation

HRID 724096 reaction equation
[N+:1]([O-:4])(O)=[O:2].C([O:13][C@H:14]1[CH2:17][C@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:15]1)(=O)C1C=CC=CC=1.S(=O)(=O)(O)O>C(OC(=O)C)(=O)C>[N+:1]([C:21]1[CH:22]=[CH:23][C:18]([C@H:16]2[CH2:15][C@H:14]([OH:13])[CH2:17]2)=[CH:19][CH:20]=1)([O-:4])=[O:2]

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 178525789HCID 178525789, compound

Product 1

HCID 178526628HCID 178526628, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent2×

Procedure

To a mixture of nitric acid (fuming, 2.3 mL) and acetic anhydride (25 mL) was added dropwise a mixture of trans-3-phenylcyclobutyl benzoate (step 2, 3.7 g, 24.6 mmol) and sulfuric acid in acetic anhydride (25 mL) at −23° C. The resulting mixture was stirred in an ice-bath for 1.5 h. The mixture was poured into ice water (200 mL) and extracted with dichloromethane (2×100 mL). The organic layer was washed with water and brine (100 mL), then dried (Na2SO4), and concentrated. The oily residue was dissolved in methanol (100 mL), and 4N aqueous LiOH (50 mL) was added. The resulting mixture was stirred at room temperature for 10 min, then concentrated. The residue was dissolved in water (100 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated. Purification by flash column chromatography on silica gel eluting with hexane/ethyl acetate (2:1) to afford 2.7 g (56%) of the title compound as a pale yellow oil: MS (EI) m/z 193 (M+); 1H-NMR (CDCl3) δ 8.18 (2H, d, J=8.6 Hz), 7.38 (2H, d, J=8.6 Hz), 4.62–4.52 (1H, m), 3.81–3.71 (1H, m), 2.54–2.45 (4H, m).

Workup

  1. additionwas added dropwise
  2. extractionextracted with dichloromethane (2×100 mL)
  3. washThe organic layer was washed with water and brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe oily residue was dissolved in methanol (100 mL)
  7. addition4N aqueous LiOH (50 mL) was added
  8. stirringThe resulting mixture was stirred at room temperature for 10 min
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in water (100 mL)
  11. extractionextracted with ethyl acetate (100 mL)
  12. washThe organic layer was washed with brine
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated
  15. customPurification by flash column chromatography on silica gel eluting with hexane/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-a1e3221705284c60939824e1c0efb1a1
Source dataset
uspto-grants-2006_11
Patent number
US07141580B2

Reaction notes

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