Acetic Acid → Ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate

HRID 2204576Notes

Reaction equation

HRID 2204576 reaction equation
[CH2:1]([CH:3]1[CH2:7][C:6](=O)[CH2:5][CH:4]1[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2].CC(O)=O.[CH2:18]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH2:26]([N:25]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:6]1[CH2:5][CH:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:3]([CH2:1][CH3:2])[CH2:7]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7656DibenzylamineHCID 516892Sodium Bicarbonate2×HCID 5049666Sodium triacetoxyborohydrideHCID 58010012Cyclopentanecarboxylic acid, 2-ethyl-4-oxo-, ethyl ester

Product 1

HCID 58009964Ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round-bottom flask was charged with ethyl 2-ethyl-4-oxocyclopentanecarboxylate (95.9 g, 521 mmol) and DCE (1.8 L). The solution was cooled to about 0° C. and glacial AcOH (45 mL, 780 mmol) and dibenzylamine (120 mL, 625 mmol) were added drop-wise, resulting in formation of a thick suspension. The reaction mixture was warmed to about 10° C. by removing the cooling bath and additional DCE (500 mL) was added. Sodium triacetoxyborohydride (166 g, 781 mmol) was added portion-wise and the reaction mixture was stirred at room temperature for about 20 h. The reaction mixture was slowly poured into stirred saturated aqueous NaHCO3 (1.5 L), followed by the portion-wise addition of solid NaHCO3 (175 g, 2083 mmol). The mixture was stirred for about 2 h and the organic layer was separated, dried over anhydrous Na2SO4, and concentrated to dryness under reduced pressure. The crude yellow oil was purified on silica gel column chromatography eluting with a gradient of 0-20% EtOAc/heptane. The solvent was removed under reduced pressure to yield ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate (136.6 g, 72%) as a white solid: LC/MS (Table 2, Method a) Rt=3.26 min; MS m/z: 366 (M+H)+.

Workup

  1. customresulting in formation of a thick suspension
  2. temperatureThe reaction mixture was warmed to about 10° C.
  3. customby removing the cooling bath and additional DCE (500 mL)
  4. additionwas added
  5. additionThe reaction mixture was slowly poured
  6. stirringThe mixture was stirred for about 2 h
  7. customthe organic layer was separated
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe crude yellow oil was purified on silica gel column chromatography
  11. washeluting with a gradient of 0-20% EtOAc/heptane
  12. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c8fe07152f3e49538aa02b2b28d3bff8
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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