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

HRID 1487778Notes

Reaction equation

HRID 1487778 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 chromatography (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 chromatography (10 to 40% EtOAc in Hexanes gradient)

Sources & evidence

ORD record
ord-46a85ad4889c494c8c23acccf08d16d2
Source dataset
uspto-grants-2016_08
Patent number
US09428522B2

Reaction notes

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