tert-Butanol → HCID 18426153, compound

HRID 133577Notes

Reaction equation

HRID 133577 reaction equation
C([N:3]([CH2:6]C)CC)C.[Cl:8][C:9]1[CH:24]=[CH:23][C:12]([CH2:13][N:14]2[CH2:22][CH2:21][CH2:20][CH:16](C(O)=O)[CH2:15]2)=[CH:11][CH:10]=1.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:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]2[CH2:22][CH2:21][CH2:20][CH:16]([NH:3][C:6]([O:46][C:43]([CH3:45])([CH3:44])[CH3:42])=[O:32])[CH2:15]2)=[CH:23][CH:24]=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

Triethylamine (3.38 g) and activated 3 Å molecular sieve (30 g) were added to a tBuOH (500 mL) solution of 1-(4-chlorobenzyl)nipecotic acid (7.06 g, 27.8 mmol). Diphenylphosphoryl azide (8.58 g) was added, and the resulting reaction mixture was stirred under reflux for 18 hour and cooled. The solvent was removed under reduced pressure. The obtained residue was then dissolved in ethyl acetate (500 mL), and the organic layer was washed with a saturated aqueous solution of NaHCO3 (100 mL×2) and brine (50 mL), then dried (over Na2SO4) and concentrated under reduced pressure. The obtained crude product was purified by chromatography (SiO2, 25% ethyl acetate-hexane) to provide 1-(4-chlorobenzyl-3-[(tert-butoxycarbonyl)amino]piperidine (2.95 g, 32.6%) as a white crystalline solid. 1H NMR (CDCl3, 300 MHz) δ 1.4-1.75 (br, 4H), 2.2-2.7 (br, 4H), 3.5 (br, 2H), 3.8 (br, 4H), 7.3 (br, 4H). The purity was determined by RPLC/MS (>99%). ESI/MS m/e 269.2 (M++H-56, C17H26ClN2O2).

Workup

  1. customthe resulting reaction mixture
  2. temperatureunder reflux for 18 hour
  3. temperaturecooled
  4. customThe solvent was removed under reduced pressure
  5. dissolutionThe obtained residue was then dissolved in ethyl acetate (500 mL)
  6. washthe organic layer was washed with a saturated aqueous solution of NaHCO3 (100 mL×2) and brine (50 mL)
  7. dry with materialdried (over Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained crude product
  10. customwas purified by chromatography (SiO2, 25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-49c18e195a37497bb885e588b8219cdc
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

Loading…