1-Piperidinepropanoic acid, 3-(ethoxycarbonyl)-, ethyl ester → 1-Azabicyclo(3.3.1)nonan-4-one

HRID 37809Notes

Reaction equation

HRID 37809 reaction equation
CC(C)([O-])C.[K+].C(OC(=O)[CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH2:16][CH:15]([C:19]([O:21]CC)=O)[CH2:14]1)C>C1(C)C=CC=CC=1>[N:13]12[CH2:14][CH:15]([CH2:16][CH2:17][CH2:18]1)[C:19](=[O:21])[CH2:11][CH2:12]2

Participants

4

Reactant 2

HCID 115651151-Piperidinepropanoic acid, 3-(ethoxycarbonyl)-, ethyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 4178971-Azabicyclo(3.3.1)nonan-4-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A suspension of potassium tert-butoxide (12.03 g, 107 mmol; Aldrich) in toluene (200 mL) was heated to reflux for 15 minutes, then a solution of ethyl 1-(3-ethoxy-3-oxopropyl)piperidine-3-carboxylate (10.70 g, 41.6 mmol; Example 35A) in toluene (50 mL) was added dropwise over 2 hour to the refluxing reaction mixture. After the addition was complete, the reaction was heated to reflux for an additional 2 hours, cooled to ambient temperature, and extracted with water (3×50 mL). The combined aqueous layers were acidified with concentrated hydrochloric acid (40 mL), then heated to reflux for 22 hours. The reaction was basified with 45 weight % potassium hydroxide (˜35 mL) and extracted with chloroform (3×100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.50-1.81 (m, 2 H), 1.90-1.96 (m, 2 H), 2.39-2.43 (m, 1 H), 2.49-2.54 (m, 2 H), 3.08-3.41 (m, 6 H); MS (DCI/NH3) m/z 140 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 15 minutes
  3. additionAfter the addition
  4. temperaturethe reaction was heated
  5. temperatureto reflux for an additional 2 hours
  6. extractionextracted with water (3×50 mL)
  7. temperatureheated
  8. temperatureto reflux for 22 hours
  9. extractionextracted with chloroform (3×100 mL)
  10. dry with materialThe combined organic extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-df794949ed9144a4b96258db4e0a58a6
Source dataset
uspto-grants-2013_09
Patent number
US08524703B2

Reaction notes

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