Sodium hydride → Methyl 1-(4-aminophenyl)cyclopentane-1-carboxylate

HRID 1668810Notes

Reaction equation

HRID 1668810 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:16])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=1.I[CH:18]([CH:20](I)[CH3:21])[CH3:19].O.O.[Sn](Cl)(Cl)(Cl)Cl>CN(C=O)C.CCO>[CH3:3][O:4][C:5]([C:6]1([C:7]2[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=2)[CH2:21][CH2:20][CH2:18][CH2:19]1)=[O:16]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 270191Methyl p-nitrophenylacetateHCID 230423272,3-DiiodobutaneHCID 85782573Tin tetrachloride dihydrate

Product 1

HCID 15086389Methyl 1-(4-aminophenyl)cyclopentane-1-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Sodium hydride (2.8 g, 60% dispersion in mineral oil) was added slowly to a solution of (4-nitro-phenyl)-acetic acid methyl ester (6.0 g, 30.7 mmol) in anhydrous DMF (30 mL) under nitrogen at a temperature in the range of 0° C. to 10° C. After stirring at a temperature in the range of 0° C. to 10° C. for 20 min, diiodobutane (7.86 mL, 61 mmol) was added drop-wise under stirring. After complete addition, the reaction mixture was warmed to a temperature in the range of 15° C. to 40° C. and stirring continued for an additional 3 hours. The reaction was quenched by adding water slowly. The mixture was extracted by ethyl acetate (3×40 mL). The combined organic extracts were washed with water, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resultant gummy material was purified by column chromatography over silica gel to afford a pale yellow thick liquid which solidified on standing at a temperature in the range of 15° C. to 40° C. (4.1 g, 54% yield). The solid (3.4 g, 13.6 mmol) was dissolved in anhydrous EtOH and tin chloride dihydrate (13.86 g, 61 mmol) was added slowly under nitrogen. Thereafter, the mixture was heated at 90° C. for 3 hours. After evaporation of volatiles under reduced pressure, the resultant mixture was diluted with ice-water and aqueous sodium hydroxide was added to adjust pH ˜11. The mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to afford the title compound as a granular light yellow solid (2.67 g, 88% yield).

Workup

  1. stirringunder stirring
  2. additionAfter complete addition
  3. temperaturethe reaction mixture was warmed to a temperature in the range of 15° C. to 40° C.
  4. stirringstirring
  5. waitcontinued for an additional 3 hours
  6. customThe reaction was quenched
  7. additionby adding water slowly
  8. extractionThe mixture was extracted by ethyl acetate (3×40 mL)
  9. washThe combined organic extracts were washed with water, brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe resultant gummy material was purified by column chromatography over silica gel
  14. customto afford a pale yellow thick liquid which
  15. customon standing at a temperature in the range of 15° C. to 40° C. (4.1 g, 54% yield)
  16. customAfter evaporation of volatiles under reduced pressure
  17. additionthe resultant mixture was diluted with ice-water and aqueous sodium hydroxide
  18. additionwas added
  19. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  20. washThe combined organic extracts were washed with water, brine
  21. dry with materialdried over Na2SO4
  22. filtrationfiltered
  23. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ad9a35c9b9364e8bafd4911a32120dc9
Source dataset
uspto-grants-2011_08
Patent number
US07989463B2

Reaction notes

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