Hydrochloric Acid → 1-Benzylazocan-5-one

HRID 2382986Notes

Reaction equation

HRID 2382986 reaction equation
[K].CC(O)(C)C.[CH2:7]([N:14]([CH2:23][CH2:24][CH2:25][C:26]([O:28]CC)=O)[CH2:15][CH2:16][CH2:17]C(OCC)=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl>C1(C)C(C)=CC=CC=1>[CH2:7]([N:14]1[CH2:15][CH2:16][CH2:17][C:26](=[O:28])[CH2:25][CH2:24][CH2:23]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 264858diethyl 4,4'-(benzylimino)dibutanoateHCID 5462222Potassium

Product 1

HCID 594329791-Benzylazocan-5-one

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent2×

Procedure

To a stirred boiling slurry made from potassium (1.28 g, 32.8 mmol) and t-BuOH (2.43 g, 32.8 mmol) in xylene (182.5 mL) under N2 was added diethyl 4,4′-(benzylazanediyl)dibutanoate (O2) (5 g, 14.9 mmol) over 5 hrs in xylene (37.25 mL). The mixture was stirred and heated at reflux for 1 hr. After being cooled, the reaction mixture was neutralized with 6N HCl (100 mL) and then was extracted with 6N HCl (3×50 mL). The combined acid solutions were filtered and the filtrate was heated under reflux for 1 hr. After cooling, the mixture was basified with concentrated KOH solution to pH 10 with cooling and extracted with dichloromethane. The combined organics were dried over Na2SO4 and concentrated to give a residue. Another 17 batches were done in parallel. The combined residue from 18 batches was purified together by column (P.E./EtOAc 5:1) to give 1-benzylazocan-5-one (O3). 1H NMR (CDCl3, 400 MHz) δ 7.30-7.33 (m, 2H), 7.21-7.25 (m, 3H), 3.56 (s, 2H), 2.55 (t, J=6.0, 4H), 2.24 (t, J=6.4 Hz, 4H), 1.86-1.91 (m, 4H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hr
  3. temperatureAfter being cooled
  4. extractionwas extracted with 6N HCl (3×50 mL)
  5. filtrationThe combined acid solutions were filtered
  6. temperaturethe filtrate was heated
  7. temperatureunder reflux for 1 hr
  8. temperatureAfter cooling
  9. temperaturewith cooling
  10. extractionextracted with dichloromethane
  11. dry with materialThe combined organics were dried over Na2SO4
  12. concentrationconcentrated
  13. customto give a residue
  14. customThe combined residue from 18 batches was purified together by column (P.E./EtOAc 5:1)

Sources & evidence

ORD record
ord-cb72f34b616d469bbbb7a4cf9149af44
Source dataset
uspto-grants-2012_09
Patent number
US08263605B2

Reaction notes

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