Hydrochloric Acid → 2-(Trimethylsilyl)ethyl 4-[2-azido-1-(4-bromophenyl)ethyl]piperidinecarboxylate

HRID 271141Notes

Reaction equation

HRID 271141 reaction equation
Cl.O1CCOCC1.[N:8]([CH2:11][CH:12]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])(C)C)=[O:27])[CH2:22][CH2:21]1)[C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=1)=[N+:9]=[N-:10].C(=O)([O-])[O-].[K+].[K+].C(=O)(OC1C=CC([N+]([O-])=O)=CC=1)OC[CH2:42][Si:43](C)([CH3:45])[CH3:44]>>[N:8]([CH2:11][CH:12]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][CH2:32][Si:43]([CH3:45])([CH3:44])[CH3:42])=[O:27])[CH2:22][CH2:21]1)[C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=1)=[N+:9]=[N-:10]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 30861164-Nitrophenyl 2-(trimethylsilyl)ethyl carbonateHCID 17952441Tert-butyl 4-[2-azido-1-(4-bromophenyl)ethyl]piperidinecarboxylate

Product 1

HCID 179524432-(Trimethylsilyl)ethyl 4-[2-azido-1-(4-bromophenyl)ethyl]piperidinecarboxylateYield 75.4%

Procedure

Preparation 1-B: A solution of hydrogen chloride in 1,4-dioxane (4 M, 60 mL, 240 mmol) was added to tert-butyl 4-[2-azido-1-(4-bromophenyl)ethyl]piperidinecarboxylate 13 (2.5 g, 6.1 mmol). The reaction mixture was stirred at room temperature for 1 h. The solvent was evaporated under reduced pressure. The residue containing 4-[2-azido-1-(4-bromophenyl)ethyl]piperidine hydrochloride 14 was dissolved in a 50% v/v aqueous tetrahydrofuran solution (68 mL). Potassium carbonate (2.12 g, 15.3 mmol) and 2-(trimethylsilyl)ethyl p-nitrophenyl carbonate (1.74 g, 61.4 mmol) were added. The reaction mixture was stirred at room temperature for 3 h. Organic solvent was evaporated under reduced pressure. Ethyl acetate was added. The organic layer was washed with aqueous sodium bicarbonate solution, water and brine. The organic layer was dried over sodium sulfate. The solvent was evaporated under reduced pressure. The crude product was purified by flash column chromatography eluted with ethyl acetate-hexanes (1:5 v/v) to afford 2-(trimethylsilyl)ethyl 4-[2-azido-1-(4-bromophenyl)ethyl]piperidinecarboxylate 15 (2.1 g, 4.6 mmol). MS (LCMS-Electrospray) 454.1 MH+.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionThe residue containing 4-[2-azido-1-(4-bromophenyl)ethyl]piperidine hydrochloride 14
  3. dissolutionwas dissolved in a 50% v/v aqueous tetrahydrofuran solution (68 mL)
  4. stirringThe reaction mixture was stirred at room temperature for 3 h
  5. customOrganic solvent was evaporated under reduced pressure
  6. additionEthyl acetate was added
  7. washThe organic layer was washed with aqueous sodium bicarbonate solution, water and brine
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe crude product was purified by flash column chromatography
  11. washeluted with ethyl acetate-hexanes (1:5 v/v)

Sources & evidence

ORD record
ord-b580d60e736f4826be4c58fabb241a23
Source dataset
uspto-grants-2008_11
Patent number
US07452891B2

Reaction notes

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