Ethyl 4-piperidinecarboxylate → Ethyl 1-{[4-(2-ethyl-1,2,3,4-tetraazol-5-yl)phenyl]methyl}piperidine-4-carboxylate

HRID 902102Notes

Reaction equation

HRID 902102 reaction equation
[NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:30]=[N:31][N:32]([CH2:34][CH3:35])[N:33]=2)=[CH:25][CH:24]=1>CS(C)=O.CO.C(OCC)(=O)C>[CH2:34]([N:32]1[N:31]=[N:30][C:29]([C:26]2[CH:27]=[CH:28][C:23]([CH2:22][N:1]3[CH2:2][CH2:3][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:10][CH2:11]3)=[CH:24][CH:25]=2)=[N:33]1)[CH3:35]

Participants

7

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 686826535-[4-(Bromomethyl)phenyl]-2-ethyl-1,2,3,4-tetraazole

Product 1

HCID 21260416Ethyl 1-{[4-(2-ethyl-1,2,3,4-tetraazol-5-yl)phenyl]methyl}piperidine-4-carboxylateYield 71.6%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 16.0 grams (0.102 mole) of ethyl isonipecotate in 50 mL of DMSO and 66 mL of methanol was stirred, and 44 mL (0.256 mole) of N,N-diisopropylethylamine, followed by 22.8 grams (0.085 mole) of 5-[4-(bromomethyl)phenyl]-2-ethyl-1,2,3,4-tetraazole were added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 72 hours. After this time, the reaction mixture was diluted with 130 mL of ethyl acetate, and washed with a 1:1 solution of an aqueous solution saturated with sodium chloride and water. The organic layer was then washed with an aqueous solution saturated with sodium chloride and water, dried with sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using mixtures of methylene chloride and acetone. The appropriate fractions were combined and concentrated under reduced pressure, yielding 20.9 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionwere added
  2. additionUpon completion of addition
  3. washwashed with a 1:1 solution of an aqueous solution saturated with sodium chloride and water
  4. washThe organic layer was then washed with an aqueous solution saturated with sodium chloride and water
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure to a residue
  8. customThe residue was purified with column chromatography on silica gel using mixtures of methylene chloride and acetone
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a11103a3355e47d2ba6b6aaa37ed16d6
Source dataset
uspto-grants-2008_04
Patent number
US07365082B2

Reaction notes

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