Benzylamine → 5-Benzyl-5-azaspiro[2.4]heptane-4,7-dione

HRID 1366512Notes

Reaction equation

HRID 1366512 reaction equation
[C:1]([C:4]1([C:7]([O:9]CC)=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].BrBr.[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CCO>[C:15]1([CH2:14][N:21]2[CH2:2][C:1](=[O:3])[C:4]3([CH2:5][CH2:6]3)[C:7]2=[O:9])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 24408BromineHCID 234183Ethyl 1-acetylcyclopropane-1-carboxylate

Product 1

HCID 98777875-Benzyl-5-azaspiro[2.4]heptane-4,7-dioneYield 26.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of ethyl 1-acetylcyclopropanecarboxylate (7.6482 g, 48.97 mmol) in EtOH (54 mL) was slowly added bromine (2.76 mL, 53.87 mmol) via syringe. The orange solution was stirred for 2 h and then concentrated in vacuo. To a 0° C. solution of the residue in EtOH (54 mL) was added benzylamine (13.4 mL, 122.7 mmol) slowly via syringe, and the mixture was stirred and warmed to room temperature overnight. The mixture was concentrated in vacuo and partitioned between DCM (200 mL) and 1 N aq. HCl (100 mL). The aqueous phase was extracted with a fresh portion of DCM (100 mL), and the combined organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (40% EtOAc in hexanes) to afford 5-(phenylmethyl)-5-azaspiro[2.4]heptane-4,7-dione (2.7842 g, 26%) as a yellow solid. LCMS: (M+H)+: 216.1.

Workup

  1. concentrationconcentrated in vacuo
  2. stirringthe mixture was stirred
  3. concentrationThe mixture was concentrated in vacuo
  4. custompartitioned between DCM (200 mL) and 1 N aq. HCl (100 mL)
  5. extractionThe aqueous phase was extracted with a fresh portion of DCM (100 mL)
  6. dry with materialthe combined organic phase was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9011beefd9dc4a86b4b8cafb68883873
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…