Sodium hydride → Benzyl 3-(4-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

HRID 2363049Notes

Reaction equation

HRID 2363049 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:8]2([CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:10][CH2:9]2)[N:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:6][NH:5]1.Br[CH2:31][C:32]1[CH:44]=[CH:43][C:35]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:34][CH:33]=1>CN(C)C=O>[C:39]([O:38][C:36]([C:35]1[CH:43]=[CH:44][C:32]([CH2:31][N:5]2[C:4](=[O:3])[C:8]3([CH2:9][CH2:10][N:11]([C:14]([O:16][CH2:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[O:15])[CH2:12][CH2:13]3)[N:7]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:6]2)=[CH:33][CH:34]=1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11414578Tert-butyl 4-(bromomethyl)benzoateHCID 58046755Benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 58046739Benzyl 3-(4-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylateYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in oil, 0.46 g, 0.0114 mol) was added portionwise at 0° C. to benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (4.00 g, 0.0109 mol) in N,N-dimethylformamide (40 mL) and the mixture stirred at 0° C. for 10 minutes. tert-Butyl 4-(bromomethyl)benzoate (3.27 g, 0.0120 mol) was added dropwise at 0° C., the mixture then allowed to warm to room temperature, and stirred for 2 hours. The reaction was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extracts were washed with brine, dried (MgSO4), and evaporated. The residue was purified by Biotage flash column chromatography (gradient 0 to 30% ethyl acetate/hexanes) to give product as an oil (4.97 g, 82%); 1H NMR (DMSO-d6); 61.53 (s, 9H); 1.72 (d, J=13.6 Hz, 2H); 2.34-2.42 (m, 2H); 3.57 (m, 2H); 3.99-4.03 (m, 2H); 4.61 (s, 2H); 4.63 (s, 2H); 6.69 (d, J=8 Hz, 2H); 6.78 (t, J=7.2 Hz, 1H); 7.18 (dd, J=7.2 Hz and 8.8 Hz, 2H); 7.32-7.39 (m, 5H); 7.42 (d, J=8.4 Hz, 2H); 7.90 (d, J=8.4 Hz, 2H);

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 2 hours
  3. customThe reaction was quenched with 2M aqueous hydrochloric acid
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by Biotage flash column chromatography (gradient 0 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a36c1a308717455fbb47b0c057761e5e
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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