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

HRID 2370024Notes

Reaction equation

HRID 2370024 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 dropwise. After addition, the stirring solution became milky, and a white precipitate 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. 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, 5H), 5.26-4.97 (m, 2H), 4.34-4.06 (m, 3H), 4.06-3.91 (m, 1H), 3.13 (br. s., 1H), 2.96-2.81 (m, 1H), 2.46 (br. s., 1H), 2.15-1.96 (m, 1H), 1.78-1.56 (m, 2H), 1.49 (br. s., 1H), 1.33-1.17 (m, 3H).

Workup

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

Sources & evidence

ORD record
ord-151f96ccc2564e71bbab123ee313f608
Source dataset
uspto-grants-2014_04
Patent number
US08710049B2

Reaction notes

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