Benzyl Bromide → Ethyl-1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylate

HRID 962730Notes

Reaction equation

HRID 962730 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([N:19]1[CH2:24][CH2:23][CH:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1.Cl.C(OCC)(=O)C>[C:11]([N:19]1[CH2:24][CH2:23][C:22]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]1)(=[O:18])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 3

HCID 7498Benzyl BromideHCID 735824Ethyl 1-benzoylpiperidine-4-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 10545888Ethyl-1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylate

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 176 mL of commercial 1M lithium bistrimethylsilylamide in tetrahydrofuran was diluted with 100 mL of tetrahydrofuran and cooled to -78° C. under inert atmosphere. A solution of 44 g of ethyl 1-benzoyl-4-piperidinecarboxylate in 200 mL of tetrahydrofuran was added dropwise keeping the temperature below -60° C., followed by 21 mL of benzyl bromide. The resulting mixture was allowed to warm and stir overnight, diluted with 200 mL of 1N hydrochloric acid, 200 mL of ethyl acetate and separated. The organic layer was washed with 200 mL of 1N hydrochloric acid, dried over MgSO4, and concentrated. The residue was dissolved in 300 mL of toluene, filtered and concentrated under reduced pressure. Drying under reduced pressure gave 56.3 g of ethyl 1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylate as a viscous oil homogeneous by thin layer chromatography, eluting with 1:1 ethyl acetate: hexane, 1H NMR (300 MHz, CDCl3) 1.20 (t, 3H), 1.40 (m, 1H), 1.60 (m, 1H), 2.07 (m, 1H), 2.22 (m, 1H), 2.85 (d, 2H), 3.08 (m, 1H), 3.65 (m, 1H), 4.12 (q, 2H), 4.65 (m, 1H), 7.04 (m, 2H), 7.24 (m, 3H), 7.38 (m, 5H).

Workup

  1. customthe temperature below -60° C.
  2. temperatureto warm
  3. customseparated
  4. washThe organic layer was washed with 200 mL of 1N hydrochloric acid
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in 300 mL of toluene
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customDrying under reduced pressure

Sources & evidence

ORD record
ord-6d23b3f6273848aa891bf1bb8d8c5a54
Source dataset
uspto-grants-1998_06
Patent number
US05760054

Reaction notes

Loading…