Potassium Carbonate → (3R,4S)-3-(1-phenyl-ethylamino)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

HRID 1169213Notes

Reaction equation

HRID 1169213 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C@@H:7]1[NH:19][C@@H:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:21])=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:8][C@@H:7]1[NH:19][CH:20]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH3:21])=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 53362444(3R,4R)-3-[(R)-1-phenyl-ethylamino]-piperidine-1,4-dicarboxylic acid 1-tert-butyl Ester 4-ethyl Ester

Product 1

HCID 69748453(3R,4S)-3-(1-phenyl-ethylamino)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl esterYield 15%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a dry flask (3R,4R)-3-[(R)-1-phenyl-ethylamino]-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (31.32 g, 83.0 mmol) was dissolved in ethanol (400 mL). Potassium carbonate (68.72 g) was added and the mixture was refluxed for 6 hours. The reaction mixture was cooled, filtered through a bed of celite, and concentrated in vacuo to give a crude oil. Purification by flash column chromatography (20-50% ethyl acetate/hexanes) provided a colorless oil (4.59 g, 15%). Unepimerized ester was also isolated (23.49 g, 75%). 1H NMR (300 MHz, CDCl3), δ: 7.25 (t, J=5, 2H), 7.245 (t, J=2, 2H), 7.20 (d, J=5, 1H), 4.19 (q, J=7, 2H), 3.94 (bd, J=13, 2H), 3.86 (m, 2H), 2.85 (m, 1H), 2.71 (m, 2H), 2.32 (d, J=7, 2H), 2.20 (d, J=15, 1H), 1.68 (bs, 3H), 1.51 (s, 9H). MS (ESI), m+/z: (M+H)+=377.

Workup

  1. temperaturethe mixture was refluxed for 6 hours
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through a bed of celite
  4. concentrationconcentrated in vacuo
  5. customto give a crude oil
  6. customPurification by flash column chromatography (20-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-da4fdd9bcdf648b6a5dc59d553aa371d
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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