Sodium Carbonate → Benzyl ethyl piperidine-1,3-dicarboxylate

HRID 2409900Notes

Reaction equation

HRID 2409900 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1.C([O-])([O-])=O.[Na+].[Na+].[C:18](Cl)(=[O:27])[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1.O>[N:1]1([C:18]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:27])[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 98969Ethyl nipecotate

Product 1

HCID 17999271Benzyl ethyl piperidine-1,3-dicarboxylateYield 80.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl piperidine-3-carboxylate (4 g, 25.4 mmol) in THF (30 mL) and water (30.0 mL) was added Na2CO3 (6.74 g, 63.6 mmol). The resulting suspension was stirred at rt for 20 min. After this time, benzyl carbonochloridate (4.12 g, 24.17 mmol) was added in dropwise. After addition, the stirring solution became milky, then white precipitates formed. After stirring at rt for 2 h, the reaction was partitioned between EtOAc and water. The separated aqueous phase was extracted with EtOAc (2×). The combined organics were washed with water and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered and concentrated to dryness. The oily residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-40% EtOAc/Hex. The desired fractions were concentrated to afford the desired product, 1-benzyl 3-ethyl piperidine-1,3-dicarboxylate (5.68 g, 19.50 mmol, 77% yield) as a colorless oil. Anal. Calcd. for C16H21NO4 m/z 291.3, found: 292.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.41-7.28 (m, 5 H), 5.26-4.97 (m, 2 H), 4.34-4.06 (m, 3 H), 4.06-3.91 (m, 1 H), 3.13 (br. s., 1 H), 2.96-2.81 (m, 1 H), 2.46 (br. s., 1 H), 2.15-1.96 (m, 1 H), 1.78-1.56 (m, 2 H), 1.49 (br. s., 1 H), 1.33-1.17 (m, 3 H).

Workup

  1. additionAfter addition
  2. customwhite precipitates
  3. customformed
  4. stirringAfter stirring at rt for 2 h
  5. customthe reaction was partitioned between EtOAc and water
  6. extractionThe separated aqueous phase was extracted with EtOAc (2×)
  7. washThe combined organics were washed with water and saturated aqueous NaCl
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe oily residue was purified
  12. washeluting with a gradient of 0-40% EtOAc/Hex
  13. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-ba12c86755504c2a8e4aab373f40f3ee
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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