Acetic Acid → HCID 15035851, compound

HRID 1195230Notes

Reaction equation

HRID 1195230 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:10]([OH:13])(=O)[CH3:11].[CH2:14]=O.[CH2:16]([N:23]1[CH2:28]C[C:26](=O)[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CO>[CH2:1]([N:8]1[CH2:14][CH:25]2[CH2:26][CH:11]([CH2:28][N:23]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:24]2)[C:10]1=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 176Acetic Acid2×HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 7504BenzylamineHCID 192201-Benzyl-4-piperidone

Product 1

HCID 15035851HCID 15035851, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A 500-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer, a heating mantle, a standard condenser with a N2 inlet, a 250-mL addition funnel, and a glass stopper. A mixture of benzylamine (10.71 g, 100 mmol), HCl (37%, 4.93 g, 50 mmol), glacial acetic acid (6.0 g, 100 mmol) and paraformaldehyde (6.31 g, 210 mmol) in CH3OH (100 mL) was brought to gentle reflux with stirring under N2 over 15 min. A solution of 1-benzyl-4-piperidinone (43, 18.93 g, 100 mmol) and glacial acetic acid (6.01 g, 100 mmol) in CH3OH (100 mL) was then added dropwise over 1 h and this was followed by a period of reflux for an additional 18 h. Upon cooling the mixture to RT, the solvent was removed and the resulting red oil was redissolved in H2O (100 mL). Combined extracts (ether, 2×100 mL) of the acidic aqueous layer were discarded. Basification of the chilled (10° C., ice water bath) water layer to pH~12 was effected by the addition of 10% NaOH. Combined extracts (ether, 4×60 mL) were dried (Na2SO4, 1 h), filtered, and concentrated to give a viscous red oil. This oil was digested (Skelly B, 2×250 mL, 20 min), and the supernatant extracts were concentrated and then distilled (190°-215° C./10-5 mm Hg) to give an oil. Crystallization of the oil was induced by dissolving the oil in hot pentane (800 mL) and then chilling (-10° C.) the solution to give 14.66 g (45.8%) of white, crystalline ketone (19); mp 82.5°-83.5° C. Concentration (hot plate) of the mother liquor to ~80 mL produced a second crop (0.81 g, 2.5%) of 3,7-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-one (19); mp 81.5°-82.0° C. The total yield was (15.47 g, 48.3%).

Workup

  1. customA 500-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer
  2. additiona heating mantle, a standard condenser with a N2 inlet, a 250-mL addition funnel
  3. temperatureto gentle reflux
  4. waitthis was followed by a period
  5. temperatureof reflux for an additional 18 h
  6. customthe solvent was removed
  7. dissolutionthe resulting red oil was redissolved in H2O (100 mL)
  8. temperatureBasification of the chilled (10° C., ice water bath) water layer to pH~12
  9. additionwas effected by the addition of 10% NaOH
  10. dry with materialCombined extracts (ether, 4×60 mL) were dried (Na2SO4, 1 h)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a viscous red oil
  14. customSkelly B, 2×250 mL, 20 min
  15. concentrationwere concentrated
  16. distillationdistilled (190°-215° C./10-5 mm Hg)
  17. customto give an oil
  18. customCrystallization of the oil
  19. dissolutionby dissolving the oil in hot pentane (800 mL)
  20. temperaturechilling (-10° C.) the solution

Sources & evidence

ORD record
ord-2ccdf73767cd45ffb772608883bcba99
Source dataset
uspto-grants-1992_05
Patent number
US05110933

Reaction notes

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