Acetic Anhydride → 3-[2-(2-Methoxyphenyl)-ethyl]-2,4-dioxo-3,9-diaza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl Ester

HRID 987084Notes

Reaction equation

HRID 987084 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH:16]([C:17]([OH:19])=[O:18])[CH2:15][CH2:14][CH2:13][CH:12]1[C:20]([OH:22])=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[CH2:27][CH2:28][NH2:29].C(OC(=O)C)(=O)C>O1CCOCC1>[CH2:1]([O:8][C:9]([N:11]1[CH:16]2[CH2:15][CH2:14][CH2:13][CH:12]1[C:20](=[O:21])[O:18][C:17]2=[O:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([O:8][C:9]([N:11]1[CH:12]2[CH2:13][CH2:14][CH2:15][CH:16]1[C:17](=[O:19])[N:29]([CH2:28][CH2:27][C:26]1[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=1[O:24][CH3:23])[C:20]2=[O:22])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 748962-MethoxyphenethylamineHCID 12265926Piperidine-1,2,6-tricarboxylic acid 1-benzyl ester

Product 2

HCID 544831212,4-Dioxo-3-oxa-9-aza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl EsterHCID 572806073-[2-(2-Methoxyphenyl)-ethyl]-2,4-dioxo-3,9-diaza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl EsterYield 90%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2,4-Dioxo-3-oxa-9-aza-bicyclo[3.3.1]nonane-9-carboxylic acid benzyl ester (Compound 2, 1.00 g, 3.45 mmol), which was prepared from Compound 1, was dissolved in dioxane (1 mL), and 2-methoxyphenethylamine (0.50 mL, 3.45 mmol) was added from the top. The mixture was stirred at room temperature for 1 hour. After this time, acetic anhydride (0.65 mL, 6.9 mmol) was added, and the reaction was refluxed for 5 hours. Flash chromatographic purification of the residue (20% EtOAc/hexanes) gave Compound 8 (1.23 g, 90% yield) as a clear oil. Rf=0.75 (50% EtOAc/hexanes), 0.66; 1H NMR: δ 1.75-2.05 (m, 6H), 2.84-2.89 (m, 2H), 3.83 (s, 3H), 4.04-4.10 (m, 2H), 4.90 (brs, 2H), 5.16 (s, 2H), 6.78-6.83 (m, 2H), 7.05 (dd, 1H, J=7.5, 1.6), 7.13-7.20 (m, 1H), 7.33-7.41 (m, 5H).

Workup

  1. temperaturethe reaction was refluxed for 5 hours
  2. customFlash chromatographic purification of the residue (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-97d8a0596c234818be9666fe76f0b5e1
Source dataset
uspto-grants-2003_10
Patent number
US06630472B1

Reaction notes

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