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

HRID 2204568Notes

Reaction equation

HRID 2204568 reaction equation
[CH3:1][CH:2]1[CH2:6][C:5](=O)[CH2:4][CH:3]1[C:8]([O:10][CH2:11][CH3:12])=[O:9].CC(O)=O.[CH2:17]([NH:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH2:25]([N:24]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:5]1[CH2:4][CH:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:2]([CH3:1])[CH2:6]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7656DibenzylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 13089479Ethyl 2-methyl-4-oxocyclopentanecarboxylate

Product 1

HCID 58010318Ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round-bottom flask was charged with ethyl 2-methyl-4-oxocyclopentanecarboxylate (10.0 g, 58.8 mmol) and DCE (180 mL). The solution was cooled to about 0° C. and AcOH (5.7 mL, 100 mmol) and dibenzylamine (11.3 mL, 58.8 mmol) were added drop-wise, resulting in formation of a thick suspension. The reaction mixture was warmed to about 10° C. and sodium triacetoxyborohydride (21.2 g, 100 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 (300 mL) for about 20 min. The layers were separated and the aqueous phase was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine (2×100 mL), dried over anhydrous Na2SO4, and concentrated to dryness under reduced pressure. The crude yellow oil was purified via flash column chromatography eluting with a gradient of 0-30% EtOAc in heptane. The solvent was removed under reduced pressure to give ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate (15.5 g, 75%) as colorless oil: 1H NMR (pyridine-d5) δ 7.53 (dd, J=0.9, 7.9 Hz, 4H), 7.43-7.35 (m, 4H), 7.33-7.25 (m, 2H), 4.22-4.06 (m, 2H), 3.79 (d, J=14.2 Hz, 2H), 3.70 (d, J=14.2 Hz, 2H), 3.34-3.22 (m, 1H), 2.76 (dd, J=7.9, 16.6 Hz, 1H), 2.25-2.13 (m, 1H), 2.09-1.94 (m, 2H), 1.88-1.79 (m, 1H), 1.52 (dd, J=10.5, 22.5 Hz, 1H), 1.16 (t, J=7.1 Hz, 3H), 0.98 (d, J=7.0 Hz, 3H).

Workup

  1. customresulting in formation of a thick suspension
  2. temperatureThe reaction mixture was warmed to about 10° C.
  3. additionThe reaction mixture was slowly poured
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with DCM (3×100 mL)
  6. washThe combined organic extracts were washed with brine (2×100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe crude yellow oil was purified via flash column chromatography
  10. washeluting with a gradient of 0-30% EtOAc in heptane
  11. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-bb5f0c0a57bd4292b213fdff40352732
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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