Tributylphosphine → N-Boc-3-[(1-Cbz-4-piperidyl)oxy]aniline

HRID 499190

Reaction equation

HRID 499190 reaction equation
C1CCN(C(/N=N/C(N2CCCCC2)=O)=O)CC1.C(P(CCCC)CCCC)CCC.[C:32]([O:36][C:37](=[O:46])[NH:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([OH:45])[CH:40]=1)([CH3:35])([CH3:34])[CH3:33].[CH2:47]([O:54][C:55]([N:57]1[CH2:62][CH2:61][CH:60](O)[CH2:59][CH2:58]1)=[O:56])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C1COCC1>[CH2:47]([O:54][C:55]([N:57]1[CH2:62][CH2:61][CH:60]([O:45][C:41]2[CH:42]=[CH:43][CH:44]=[C:39]([NH:38][C:37]([O:36][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:46])[CH:40]=2)[CH2:59][CH2:58]1)=[O:56])[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 312485tert-butyl N-(3-hydroxyphenyl)carbamateHCID 2794620Benzyl 4-Hydroxy-1-piperidinecarboxylateHCID 5702657diazenedicarboxylic acid bis(N,N-piperidide)

Product 1

HCID 68454608N-Boc-3-[(1-Cbz-4-piperidyl)oxy]anilineYield 57.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cooled solution of 1,1-(azodicarbonyl) dipiperidine (18.08 g, 71.7 mmol) in anhydrous THF (200 mL) is added via syringe tributylphosphine (17.69 mL, 79.7 mmol) and allowed to stir for 2.5 hours. To this ice-cooled mixture is added a solution of (3-hydroxy-phenyl)-carbamic acid tert-butyl ester (10.0 g, 47.8 mmol) and 4-hydroxy-piperidine-1-carboxylic acid benzyl ester (7.23 mL, 47.8 mmol) in anhydrous THF (30 mL) causing a light yellow precipitate to form. The mixture is warmed to room temperature and stirred overnight. The mixture is filtered through a fritted funnel and washed solid with THF (3×15 mL). After removal of solvent, the residue is purified on a silica gel chromatography with ethyl acetate-hexanes to provide a clear oil (11.8 g, 57.9% yield, ES+(m/z) 427.2 [M+H]).

Workup

  1. customto form
  2. stirringstirred overnight
  3. filtrationThe mixture is filtered through a fritted funnel
  4. washwashed solid with THF (3×15 mL)
  5. customAfter removal of solvent
  6. customthe residue is purified on a silica gel chromatography with ethyl acetate-hexanes
  7. customto provide a clear oil (11.8 g, 57.9% yield, ES+(m/z) 427.2 [M+H])

Sources & evidence

ORD record
ord-daef209fb4e74236ba50d9dacf889ede
Source dataset
uspto-grants-2010_08
Patent number
US07767674B2

Linked notes

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