Benzylamine → Tert-butyl 9-benzyl-7-oxo-3,9-diazabicyclo[3.3.1]nonane-3-carboxylate

HRID 2354885Notes

Reaction equation

HRID 2354885 reaction equation
[CH2:1]([C:8](O)=O)[C:2]([CH2:4][C:5](O)=O)=[O:3].C([O-])(=O)C.[Na+].[C:16]([O:20][C:21](=[O:29])[N:22]([CH2:26]C=O)[CH2:23]C=O)([CH3:19])([CH3:18])[CH3:17].[CH2:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>O.Cl>[C:16]([O:20][C:21]([N:22]1[CH2:26][CH:8]2[N:37]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:5]([CH2:4][C:2](=[O:3])[CH2:1]2)[CH2:23]1)=[O:29])([CH3:19])([CH3:18])[CH3:17]

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 11430Potassium CarbonateHCID 68328Acetonedicarboxylic acidHCID 517045Sodium AcetateHCID 135745471,1-Dimethylethyl N,N-bis(2-oxoethyl)carbamate

Product 1

HCID 59679479Tert-butyl 9-benzyl-7-oxo-3,9-diazabicyclo[3.3.1]nonane-3-carboxylateYield 48.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

Acetone-1,3-dicarboxylic acid (13.8 g, 94.96 mmol) and sodium acetate (7.94 g, 96.8 mmol) were added to a solution of bis-(2-oxo-ethyl)-carbamic acid tert-butyl ester (19.1 g, 94.96 mmol) in H2O (118 mL). Benzylamine (10.3 mL, 94.96 mmol) was dissolved in aqueous HCl (3 N, 63 mL) and was subsequently added to the stirring solution of the dialdehyde and the dicarboxylic acid over a 15 minute period. The reaction mixture was stirred for 3 days at room temperature after which the pH was adjusted to 8 by the addition of potassium carbonate. The resulting solution was extracted with methylene chloride (4×70 mL), the organic extracts dried (Na2SO4), filtered and concentrated under vacuum. The resulting residue was purified by silica gel chromatography, (eluant hexane/EtOAc 9/1 to 1/1, v/v), to give 15.1 g (48%) of 9-benzyl-7-oxo-3,9-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester as a brown oil. Retention time (min)=1.195, method [1], MS (ESI) 331.2 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.43-7.15 (m, 5H), 4.00-3.81 (m, 4H), 3.21 (bs, 2H), 3.20-2.98 (m, 2H), 2.62 (dd, J=15.9 Hz, 5.5 Hz, 2H), 2.28-2.17 (m, 2H), 1.42 (s, 9H).

Workup

  1. extractionThe resulting solution was extracted with methylene chloride (4×70 mL)
  2. dry with materialthe organic extracts dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe resulting residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e5d038f098ec4b5c95b0a939ac996f6a
Source dataset
uspto-grants-2010_07
Patent number
US07754712B2

Reaction notes

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