Hydroxyamine hydrochloride → HCID 73067175, compound

HRID 747835Notes

Reaction equation

HRID 747835 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[C:7]([C@@:11]23[CH2:20][C@H:15]([CH2:16][C:17](=O)[CH2:18]2)[N:14]([CH3:21])[CH2:13][C@H:12]3[CH3:22])[CH:8]=[CH:9][CH:10]=1)[CH3:3].Cl.[NH2:24][OH:25]>CCO>[CH:2]([O:4][C:5]1[CH:6]=[C:7]([C:11]23[CH2:20][CH:15]([CH2:16][C:17](=[N:24][OH:25])[CH2:18]2)[N:14]([CH3:21])[CH2:13][CH:12]3[CH3:22])[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:1]

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 68807523HCID 68807523, compound

Product 1

HCID 73067175HCID 73067175, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-(3-Isopropoxy-phenyl)-2,4-dimethyl-2-aza-bicyclo[3.3.1]nonan-7-one (2.2) (3.11 g, 13.0 mmole) and hydroxylamine hydrochloride (4.50 g, 64.8 mmol) in EtOH (absolute, 195 mL) were heated to reflux for 3 h. The reaction mixture was allowed to cool to room temperature and the ethanol was removed under reduced pressure. The crude oil was dissolved in 2 N NaOH (100 mL) and extracted with 3:1 CH2Cl2/THF (4×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure yielding crude product. The crude product was purified by flash chromatography (neutral alumina, Brockman activity II-III) eluting with 9:1 ethyl acetate:hexane to afford the title compound (3.6 g, 88%) as an off white solid. 1H NMR (CDCl3) δ 8.47 (br, 1H), 7.23 (t, J=7.8 Hz, 1H), 7.00-6.72 (m, 3H), 4.54 (m, 1H), 3.63 (d, J=17 Hz, 1H), 3.29 (br, 1H), 2.94-2.85 (m, 2H), 2.51 (d, J=15.9 Hz, 1H), 2.44-2.40 (m, 4H), 2.05-1.87 (m, 5H), 1.33 (d, J=6.0 Hz, 6H), 0.76 (d, J=6.9 Hz, 3H).

Workup

  1. temperatureto reflux for 3 h
  2. customthe ethanol was removed under reduced pressure
  3. dissolutionThe crude oil was dissolved in 2 N NaOH (100 mL)
  4. extractionextracted with 3:1 CH2Cl2/THF (4×50 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customyielding crude product
  9. customThe crude product was purified by flash chromatography (neutral alumina, Brockman activity II-III)
  10. washeluting with 9:1 ethyl acetate

Sources & evidence

ORD record
ord-a49a204e40a94365a785f1005d0757ae
Source dataset
uspto-grants-2008_07
Patent number
US07399762B2

Reaction notes

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