Acetic Acid → Benzyl 4-oxo[1,4'-bipiperidine]-1'-carboxylate

HRID 2421054Notes

Reaction equation

HRID 2421054 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1.Cl.C[O:20][C:21]1(OC)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[OH-].[Na+]>ClCCCl>[O:20]=[C:21]1[CH2:26][CH2:25][N:24]([CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]2)[CH2:23][CH2:22]1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 6721521577542-16-6

Product 1

HCID 53438424Benzyl 4-oxo[1,4'-bipiperidine]-1'-carboxylateYield 66.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Benzyl 4-oxopiperidine-1-carboxylate (29.5 g, 126 mmol), 4,4-dimethoxypiperidine hydrochloride (20 g, 110 mmol), and trietylamine (16.9 mL, 1121 mmol) were stirred in 1,2-dichloroethane (600 mL). Sodium triacetoxyborohydride (30.4, 143 mmol) was added at 0° C. (over 30 minutes) followed by acetic acid (8.2 mL, 143 mmol) and the solution was stirred at room temperature for 24 h. 1N NaOH (100 mL) was added to the mixture and the solution was extracted with dichloromethane (3×100 mL). The combined organic extracts were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in acetone (300 mL) and HCl (50 mL, 5N to 6N in 2-propanol) was added and was heated at reflux overnight. The mixture was concentrated in vacuo, diluted with dichloromethane (100 ml) and extracted with HCl 1N (4×100 ml). The aqueous extracts were combined and basified with NaOH pallets. The solution was then extracted with dichloromethane (3×100 mL), combined organic extracts were dried with anhydrous sodium sulphate, filtered and concentrated in vacuo to afford the titled compound (23 g, 66%) 1H-NMR (300 MHz, CD3OD): δ 7.30 (5H, m), 5.10 (2H, s) 4.21 (2H, d, J=13.5 Hz) 2.87 (4H, t, J=6.2 Hz), 2.77-2.70 (1H, m) 2.62-2.58 (2H, m), 2.40 (2H, t, J=6.2 Hz) 1.86 (2H, d, J=12.0 Hz), 1.75 (2H, t, J=5.6 Hz) 1.42 (2H, m).

Workup

  1. extractionthe solution was extracted with dichloromethane (3×100 mL)
  2. dry with materialThe combined organic extracts were dried with anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in acetone (300 mL)
  6. additionHCl (50 mL, 5N to 6N in 2-propanol) was added
  7. temperaturewas heated
  8. temperatureat reflux overnight
  9. concentrationThe mixture was concentrated in vacuo
  10. additiondiluted with dichloromethane (100 ml)
  11. extractionextracted with HCl 1N (4×100 ml)
  12. extractionThe solution was then extracted with dichloromethane (3×100 mL)
  13. dry with materialwere dried with anhydrous sodium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-872226c0ef694696b1fd8e3085b53003
Source dataset
uspto-grants-2011_06
Patent number
US07956069B2

Reaction notes

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