Sodium Iodide → 4-[4-(1,4,7-Trioxaoct-1-yl)phenyl]-N-benzyloxycarbonylbutylamine

HRID 1516356Notes

Reaction equation

HRID 1516356 reaction equation
C([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)(OCC1C=CC=CC=1)=O.Br[CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30].[C:31](=[O:34])([O-])[O-:32].[K+].[K+].[I-].[Na+]>CC(C)=O.CN(C=O)C>[O:22]([C:19]1[CH:18]=[CH:17][C:16]([CH:15]([C:31]([O:32][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:34])[CH2:14][CH2:13][CH2:12][NH2:11])=[CH:21][CH:20]=1)[CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30]

Participants

7

Reactant 4

HCID 5238Sodium Iodide2×HCID 11430Potassium Carbonate3×HCID 1235321-Bromo-3,6-dioxaheptane3×HCID 11637991N-Cbz4-(4-hydroxyphenyl)butylamine

Product 1

HCID 673669224-[4-(1,4,7-Trioxaoct-1-yl)phenyl]-N-benzyloxycarbonylbutylamineYield 166%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6228DimethylformamideSolvent

Procedure

4-(4-Hydroxyphenye-N-benzyloxycarbonylbutylamine (29) (1.0 g, 3.3 mmol), 1-bromo-2-(2-methoxyethoxy)ethane (0.67 g, 3.7 mmol), and potassium carbonate (0.60 g, 4.3 mmol) were combined in acetone (20 mL), and stirred at reflux overnight. The reaction was allowed to cool, and then filtered and evaporated. The residue was re-subjected in methyl ethyl ketone (10 mL), 1-bromo-2-(2-methoxyethoxy)ethane (0.91 g, 5.0 mmol), potassium carbonate (0.74 g, 5.3 mmol), and sodium iodide (0.5 g, 3.3 mmol) with stirring at reflux for 2.5 h. The reaction was allowed to cool, and was filtered and evaporated. The residue was re-subjected in DMF (10 mL), with 1-bromo-2-(2-methoxyethoxy)ethane (1.8 g, 9.8 mmol), potassium carbonate (1.60 g, 11.6 mmol), and sodium iodide (0.4 g, 2.7 mmol), overnight with stirring at 70° C. The reaction was evaporated to remove the solvent and then was dissolved in ethyl acetate (70 mL). The organic extract was washed with water (3×20 mL), dried over potassium carbonate and filtered. Evaporation afforded 1.1 g of an oil which was purified by column chromatography (silica gel, 2:1 hexanes/ethyl acetate) to afford 800 mg (70%) of pure product 106. 1H NMR (300 MHz, CDCl3) d 1.42-1.68 (m, 4H), 2.55 (t, J=7.5 Hz, 2H), 3.20 (q, J=6.2 Hz, 2H), 3.39 (s, 3H), 3.55-3.60 (m, 2H), 3.69 B 3.74 (m, 2H), 3.82-3.87 (m, 2H), 4.11 (t, 5.3 Hz, 2H), 4.71 (br s, 1H), 5.09 (s, 21-2H), 6.82 (d, J=8.5 Hz, 2H), 7.05 (d, J=8.5 Hz, 2H), 7.34 (s, 5H). CI MS m/z=402 [C23H31NO5+H]+.

Workup

  1. temperatureat reflux overnight
  2. temperatureto cool
  3. filtrationfiltered
  4. customevaporated
  5. temperatureat reflux for 2.5 h
  6. temperatureto cool
  7. filtrationwas filtered
  8. customevaporated
  9. stirringwith stirring at 70° C
  10. customThe reaction was evaporated
  11. customto remove the solvent
  12. dissolutionwas dissolved in ethyl acetate (70 mL)
  13. extractionThe organic extract
  14. washwas washed with water (3×20 mL)
  15. dry with materialdried over potassium carbonate
  16. filtrationfiltered
  17. customEvaporation

Sources & evidence

ORD record
ord-665acd9cdcc74510854aba10e42a92ba
Source dataset
uspto-grants-2012_07
Patent number
US08227474B2

Reaction notes

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