Triethylamine → 4-hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-benzyl ester 3-ethyl ester

HRID 489615Notes

Reaction equation

HRID 489615 reaction equation
[CH3:1][CH2:2][O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][NH:8][CH2:7]1)=[O:5].Cl.C(N(CC)CC)C.[CH2:21]([O:28][C:29](ON1C(=O)CCC1=O)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1.O.C(OCC)(=O)C>[CH2:2]([O:3][C:4]([C:6]1[CH2:7][N:8]([C:29]([O:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:30])[CH2:9][CH2:10][C:11]=1[OH:12])=[O:5])[CH3:1]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 83172Benzyl succinimido carbonateHCID 1073153-Piperidinecarboxylic acid, 4-oxo-, ethyl ester, hydrochloride (1:1)

Product 1

HCID 690289334-hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-benzyl ester 3-ethyl esterYield 98.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 4-piperidone-3-carboxylate hydrochloride (5 g, 24.05 mmol) in THF (70 mL) and water (35 mL) at 0° C., was added triethylamine (8.7 mL, 62.5 mmol), followed by N-(benzyloxycarbonyloxy)succinimide (7.79 g, 31.27 mmol). The reaction mixture was stirred and allowed to warm to room temperature. After 3 hours the reaction mixture was diluted with water (50 mL) and ethyl acetate (100 mL) added. The aqueous phase was extracted into ethyl acetate (2×100 mL). The organic phases were combined, washed with brine (50 mL), dried (MgSO4), and the solvent removed in vacuo. The crude product was purified by column chromatography on silica gel (eluent, ethyl acetate:pentane=1:5) to give 4-hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-benzyl ester 3-ethyl ester as a colorless oil (7.26 g, 94%). MS (EI) 305 (M+).

Workup

  1. additionadded
  2. extractionThe aqueous phase was extracted into ethyl acetate (2×100 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customThe crude product was purified by column chromatography on silica gel (eluent, ethyl acetate:pentane=1:5)

Sources & evidence

ORD record
ord-a0a612587fba4b9491829a44f295bef0
Source dataset
uspto-grants-2005_12
Patent number
US06977263B2

Reaction notes

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