tert-Butanol → HCID 18426153, compound

HRID 279285Notes

Reaction equation

HRID 279285 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[CH2:15][CH2:14][CH2:13][CH:9](C(O)=O)[CH2:8]2)=[CH:4][CH:3]=1.CC[N:20]([CH2:23]C)CC.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:32])C=CC=CC=1.[CH3:42][C:43]([OH:46])([CH3:45])[CH3:44]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:15][CH2:14][CH2:13][CH:9]([NH:20][C:23]([O:46][C:43]([CH3:45])([CH3:44])[CH3:42])=[O:32])[CH2:8]2)=[CH:16][CH:17]=1

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 35450941-(4-chlorobenzyl)nipecotic acid

Product 1

HCID 18426153HCID 18426153, compoundYield 32.6%

Procedure

A solution of 1-(4-chlorobenzyl)nipecotic acid (7.06 g, 27.8 mmol) in tBuOH (500 mL) was treated with Et3N (3.38 g) and activated 3 A molecular sieves (30 g). Diphenylphosphoryl azide (8.58 g) was added, and the reaction mixture was warmed at reflux for 18 h. The mixture was cooled and the solvent was reflux for 18 h. The mixture was cooled and the solvent was remove under vacuum. The residue was dissolved in EtOAc (500 mL), and the organic phase was washed with saturated aqueous NaHCO3 (2×100 mL) and brine (50 mL), dried (Na2SO4), and concentrated in vacuo. Chromatography (SiO2, 25% EtOAc-hexane) afforded 1-(4-chlorobenzyl)-3-{(tert-butoxycarbonyl)amino}piperidine (2.95 g, 32.6%) as a white crystalline solid: 1H NMR (CDCl3, 300 MHz) δ1.4-1.75 (br, 4H), 2.2-2.7 (br, 4H), 3.5 (br, 2H), 3.8 (br, 1H), 7.3 (br, 4H); The purity was determined by RPLC/MS (>99%); ESI/MS m/e 269.2 (M++H-56, C17H26ClN2O2).

Workup

  1. temperaturethe reaction mixture was warmed
  2. temperatureat reflux for 18 h
  3. temperatureThe mixture was cooled
  4. temperaturethe solvent was reflux for 18 h
  5. temperatureThe mixture was cooled
  6. customthe solvent was remove under vacuum
  7. dissolutionThe residue was dissolved in EtOAc (500 mL)
  8. washthe organic phase was washed with saturated aqueous NaHCO3 (2×100 mL) and brine (50 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc77e8ff99c54fc98272e4ca7782f8b3
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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