Isoamyl Nitrite → Tert-butyl(1-(4-(6-(hydroxyimino)-5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate

HRID 1509090Notes

Reaction equation

HRID 1509090 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24](=[O:34])[CH2:23][CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].[N:42](OCCC(C)C)=[O:43]>C1COCC1>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:27]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24](=[O:34])[C:23](=[N:42][OH:43])[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8053Isoamyl NitriteHCID 23665647Potassium tert-butoxideHCID 123451908Tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 131734396Tert-butyl(1-(4-(6-(hydroxyimino)-5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamateYield 41.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate (1.00 g, 2.134 mmol) in anhydrous THF (30 mL) was added dropwise potassium tert-butoxide (1M in THF, 2.56 ml, 2.56 mmol) over a period of 10 min to give a deep red solution. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 30 min. To this was added dropwise isopentyl nitrite (0.286 ml, 2.134 mmol) over a period of 5 min to give a red solution. The reaction mixture was stirred at 50° C. under a nitrogen atmosphere for 1 hour then allowed to cool to room temperature and concentrated to dryness under reduced pressure. The residue was redissolved in water (5 mL), acidified with 1M HCl solution (5 mL) and extracted into ethyl acetate (3×10 mL). The combined organic phases were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified via Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 88:12 to 0:100) to give the desired product as a brown solid (436 mg, 41% yield)). 1H-NMR (500 MHz, CDCl3) δ 8.40 (1H, s), 7.40 (2H, d), 7.32 (2H, d), 7.25-7.29 (3H, m), 7.18-7.22 (2H, m), 5.04 (1H, br s), 3.38 (2H, t), 3.29 (2H, t), 2.26-2.59 (4H, br m), 2.01-2.12 (1H, m), 1.76-1.86 (1H, m), 1.15-1.45 (9H, br m). LCMS (Method A) RT=6.74 min, M+H+=498.13.

Workup

  1. customto give a deep red solution
  2. customto give a red solution
  3. stirringThe reaction mixture was stirred at 50° C. under a nitrogen atmosphere for 1 hour
  4. temperatureto cool to room temperature
  5. concentrationconcentrated to dryness under reduced pressure
  6. dissolutionThe residue was redissolved in water (5 mL)
  7. extractionextracted into ethyl acetate (3×10 mL)
  8. washThe combined organic phases were washed with water (20 mL), brine (20 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure
  12. customThe residue was purified via Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 88:12 to 0:100)

Sources & evidence

ORD record
ord-e08717e926b846caacca11b406ed3e7f
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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