Allylamine → 4-(Allylamino)-1-benzylpiperidin-2-one

HRID 1257622Notes

Reaction equation

HRID 1257622 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][C:9]1=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16]([NH2:19])[CH:17]=[CH2:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH4-].[Na+]>ClCCCl>[NH3:8].[CH2:16]([NH:19][CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9](=[O:15])[CH2:10]1)[CH:17]=[CH2:18]

Participants

7

Reactant 4

HCID 7853AllylamineHCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 224955411-Benzylpiperidine-2,4-dione

Product 2

HCID 222AmmoniaYield 0%HCID 673257434-(Allylamino)-1-benzylpiperidin-2-oneYield 1,407.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 1-benzyl-piperidine-2,4-dione (508 mg, 0.25 mmol), allylamine (188 μL, 2.50 mmol) and 4 Å molecular sieves (500 mg) in DCE (5 mL) was stirred at ambient temperature for 5 hours, then sodium triacetoxyborohydride (106 mg, 0.50 mmol) was added. The resulting mixture was stirred for 16 hours, filtered through Celite®, and concentrated under vacuum. The resulting residue was dissolved in methanol (4 mL) and sodium borohydride (114 mg, 3.00 mmol) was added. The mixture was stirred for 40 hours and then concentrated under vacuum. The residue was dissolved in DCM and washed with 5% aqueous sodium bicarbonate, and dried over sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel (gradient: 0 to 80% methanol in DCM then 0 to 60% 2M NH3 in methanol solution in DCM) to afford 430 mg (70%) of racemic 4-allylamino-1-benzyl-piperidin-2-one. 1H NMR (400 MHz, CDCl3) δ: 7.29 (m, 5H), 5.89-5.85 (m, 1H), 5.20 (m, 2H), 4.85 (s, 1H), 4.61 (m, 2H), 3.95 (s, 1H), 3.68 (m, 1H), 3.29-3.25 (m, 2H), 3.10 (m, 1H), 2.75 (ddd, 1H), 2.33 (t, 1H), 1.99 (m, 1H), 1.70-1.57 (m, 1H).

Workup

  1. stirringThe resulting mixture was stirred for 16 hours
  2. filtrationfiltered through Celite®
  3. concentrationconcentrated under vacuum
  4. dissolutionThe resulting residue was dissolved in methanol (4 mL)
  5. stirringThe mixture was stirred for 40 hours
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in DCM
  8. washwashed with 5% aqueous sodium bicarbonate
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under vacuum
  11. customThe residue was purified by column chromatography on silica gel (gradient

Sources & evidence

ORD record
ord-14c4fd50e146437fb0c13304e7fb71b9
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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