3-Hydroxypyridine → 4-Tert-butyl 1-benzyl 2-((pyridin-3-yloxy)methyl)piperazine-1,4-dicarboxylate

HRID 70202Notes

Reaction equation

HRID 70202 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:15][CH2:16][CH:17]1[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20][CH2:19][N:18]1[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31].O[C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[N:43]1[CH:44]=[CH:45][CH:46]=[C:41]([O:15][CH2:16][CH:17]2[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])[CH2:20][CH2:19][N:18]2[C:30]([O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:31])[CH:42]=1

Participants

6

Reactant 4

HCID 79713-HydroxypyridineHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 235310394-(1,1-Dimethylethyl) 1-(phenylmethyl) 2-(hydroxymethyl)-1,4-piperazinedicarboxylate

Product 1

HCID 596715754-Tert-butyl 1-benzyl 2-((pyridin-3-yloxy)methyl)piperazine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diisopropylazodicarboxylate (2.67 mL, 13.5 mmol) in THF (25 mL) was added dropwise over 1 h to a solution of 4-tert-butyl 1-benzyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate (4.52 g, 12.9 mmol), 3-hydroxypyridine (1.35 g, 14.2 mmol) and triphenylphosphine (3.55 g, 13.5 mmol) in THF (75 mL) at 15° C. After complete addition, the reaction mixture was allowed to warm to rt and stir overnight. The reaction mixture was concentrated under reduced pressure and purified by column chomatography (10 to 40% EtOAc in Hexanes gradient). This gave 0.9055 g (16%) of the title compound. Rf=0.35 in 80% EtOAc/Hexanes; LC-MS: RT=9.85 min; [M+H]+=428.2.

Workup

  1. additionAfter complete addition
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompurified by column chomatography (10 to 40% EtOAc in Hexanes gradient)

Sources & evidence

ORD record
ord-d702f43c338747bab50be8bb02b62a4c
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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