Iodoethane → 1-tert-Butyl 4-ethyl 4-benzylpiperidine-1,4-dicarboxylate

HRID 2179753Notes

Reaction equation

HRID 2179753 reaction equation
[CH:1](N(C(C)C)CC)([CH3:3])[CH3:2].[N:10]1([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:11]1.C(I)C.[CH2:31]1[CH2:35]O[CH2:33][CH2:32]1>>[CH2:33]([C:13]1([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:11][N:10]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:15][CH2:14]1)[C:32]1[CH:3]=[CH:1][CH:2]=[CH:35][CH:31]=1

Participants

5

Reactant 4

HCID 6340IodoethaneHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 162182711-tert-Butyl 4-ethyl 4-benzylpiperidine-1,4-dicarboxylate

Conditions

Temperature
-35 °C

Procedure

Diisopropyl ethylamine (6.5 ml) in dry THF (25 ml) was cooled to −10° C. then N-butyl lithium (1.6 molar, 23 ml) was added drop wise under nitrogen atmosphere and maintain the reaction at −10° C. for 45 minutes then cool the reaction to −75° C. for 15 minutes then 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (Above step 1, 5 g in 30 ml THF) was added and stirred the reaction at same temp for 30 minutes, again raise the reaction temperature to −35° C. and stirred for 45 minutes then again cool the reaction to −75° C. then ethyl iodide (3.5 g in 20 ml THF) was added drop wise and slowly allowed the reaction to room temperature and stirred the reaction at room temperature for about 12 hours. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with saturated NaHCO3 followed by brine and the organic layer dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 3% ethyl acetate in hexane as eluent to furnish the title compound as a light yellow color liquid. 1H NMR (300 MHz, CDCl3): 1.16-1.18 (t, 3H); 1.44 (s, 9H); 2.07-2.11 (m, 2H); 2.28 (s, 1H); 2.82 (s, 2H); 2.92-2.95 (m, 1H); 3.46-3.52 (m, 3H); 4.09-4.11 (m, 2H); ES Mass: 308 (100%) [M+Na].

Workup

  1. temperaturemaintain
  2. customthe reaction at −10° C. for 45 minutes
  3. temperaturethen cool
  4. customthe reaction to −75° C. for 15 minutes
  5. customthe reaction at same temp for 30 minutes
  6. stirringstirred for 45 minutes
  7. temperaturethen again cool
  8. customthe reaction to −75° C.
  9. customthe reaction to room temperature
  10. stirringstirred
  11. customthe reaction at room temperature for about 12 hours
  12. customAfter completion of the reaction (monitored by TLC)
  13. customthe reaction mixture was quenched with saturated ammonium chloride
  14. extractionextracted with ethyl acetate
  15. washThe organic layer was washed with saturated NaHCO3
  16. dry with materialthe organic layer dried over Na2SO4
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-81b68068a94a411eba5105e0b3b1bc72
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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