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

HRID 1862676Notes

Reaction equation

HRID 1862676 reaction equation
O[CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:41]I.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(#N)C.CCOCC.[Cl-].[Na+].O.[O-]S([O-])(=O)=O.[Cu+2]>[I:41][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1

Participants

10

Reactant 5

HCID 795ImidazoleHCID 807Iodine2×HCID 11776TriphenylphosphineHCID 24477Sodium ThiosulfateHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 9974426Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 24462Copper SulfateCatalystHCID 3283Diethyl EtherSolvent2×HCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Combined 4-(2-hydroxyeth-1-yl)-1-tert-butoxylcarbonylpiperidine (37.4 g, 0.16 mol, from Step B), triphenylphosphine (55 g, 0.21 mol) and imidazole (14 g, 0.21 mol) in 800 mL of 33% acetonitrile in ether. Cooled to 0° C. and added iodine (56 g, 0.22 mol) portionwise. The iodine is de-colored until the endpoint of the reaction. Diluted with 1 L of ether. Washed organic layer with 2×500 mL each of sat'd. aq. Na2S2O3, sat. aq. CuSO4 and brine. Dried over magnesium sulfate, filtered and concentrated. Triphenylphosphine oxide precipitates. Added ether and filtered the slurry through a plug of silica gel. Purified a portion of the crude material by flash chromatography (5% ethyl acetate in hexane eluent) to afford the title compound.

Workup

  1. dry with materialDried over magnesium sulfate
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customTriphenylphosphine oxide precipitates
  5. filtrationAdded ether and filtered the slurry through a plug of silica gel
  6. customPurified a portion of the crude material by flash chromatography (5% ethyl acetate in hexane eluent)

Sources & evidence

ORD record
ord-8a9e6b70728345f1b964a64cbeb5b2fc
Source dataset
uspto-grants-2003_03
Patent number
US06538002B1

Reaction notes

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