Imidazole → Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate

HRID 1095348Notes

Reaction equation

HRID 1095348 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]O)[CH2:3][CH2:2]1.[C:10]([O:14][C:15]([O:17]C(OC(C)(C)C)=O)=O)([CH3:13])([CH3:12])[CH3:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:49]I>ClCCl>[I:49][CH2:8][CH2:7][CH:4]1[CH2:3][CH2:2][N:1]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:17])[CH2:6][CH2:5]1

Participants

7

Reactant 5

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 739534-PiperidineethanolHCID 90495Di-tert-butyl dicarbonate

Product 1

HCID 9974426Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylateYield 84.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 2-piperidin-4-ylethanol (10 g, 77 mmol) and dichloromethane (190 mL) at 0° C. was added di-(tert-butyl)dicarbonate (17.7 g, 81.3 mmol). The reaction was warmed to ambient temperature and stirred 4 hours. The reaction was washed with water, 10% aqueous potassium hydrosulfate, and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to 20 g of tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate as a clear oil. This clear oil was dissolved in dichloromethane (90 mL) and added dropwise over 20 minutes at 0° C. to a suspension of triphenylphosphine (20 g, 77 mmol), imidazole (5.3 g, 77 mmol), iodine (22 g, 85 mmol), and dichloromethane (300 mL). The reaction was stirred 5 hours at ambient temperature. The reaction was filtered and the filtrate was quenched with sodium bisulfite and diluted with water. The layers were separated. The aqueous layer was extracted with additional dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to a brown oil. This oil was purified by chromatography (SiO2, 20% hexanes/ethyl acetate) to obtain 22 g of tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate as a colorless oil.

Workup

  1. washThe reaction was washed with water, 10% aqueous potassium hydrosulfate, and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to 20 g of tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate as a clear oil
  5. dissolutionThis clear oil was dissolved in dichloromethane (90 mL)
  6. stirringThe reaction was stirred 5 hours at ambient temperature
  7. filtrationThe reaction was filtered
  8. customthe filtrate was quenched with sodium bisulfite
  9. additiondiluted with water
  10. customThe layers were separated
  11. extractionThe aqueous layer was extracted with additional dichloromethane
  12. dry with materialThe combined organic layers were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated to a brown oil
  15. customThis oil was purified by chromatography (SiO2, 20% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-105bc05999cd44c4984e1acca71a3068
Source dataset
uspto-grants-2012_03
Patent number
US08138173B2

Reaction notes

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