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

HRID 2204593Notes

Reaction equation

HRID 2204593 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 AcOH (45 mL, 780 mmol) and dibenzylamine (120 mL, 625 mmol) were added drop-wise, resulting in the 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 saturated aqueous NaHCO3 (1.5 L) with stirring 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 by flash column chromatography using EtOAc/heptane as eluant (0-20% EtOAc) 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 the 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. stirringwith stirring
  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 by flash column chromatography

Sources & evidence

ORD record
ord-2f455a59f1864a0fa3ea1a8dc765d1c8
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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