tert-Butyl piperazine-1-carboxylate → HCID 178452249, compound

HRID 2206327Notes

Reaction equation

HRID 2206327 reaction equation
Cl[C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][N:3]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1>CCCCO.CCOC(C)=O>[OH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)[CH:7]=1

Participants

5

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 178516507HCID 178516507, compound

Product 1

HCID 178452249HCID 178452249, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2-chloro-4-hydroxypyridine (12.9 g, 100 mmol) in n-BuOH (50 mL) was added t-butyl piperazine-1-carboxylate (46.5 g, 250 mmol). The mixture was heated at 140° C. for 3 days and then diluted with EtOAc (2 L) at ambient temperature. The organic phase was washed with saturated NH4Cl solution and then brine. The organic layer was separated, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography (5%-20% MeOH/CH2Cl2) to give 12.2 g (44%) of t-butyl 4-(4-hydroxypyridin-2-yl)piperazine-1-carboxylate as a white solid. MS m/z 280.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.72 (1H, d, J=6.62 Hz), 6.20 (1H, dd, J=6.31, 2.21 Hz), 6.02 (1H, d, J=1.89 Hz), 3.56 (4H, m), 3.42 (4H, m), 1.50 (9H, s).

Workup

  1. washThe organic phase was washed with saturated NH4Cl solution
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (5%-20% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8c6c19d3e1d641d3ad7b9405c9cfb760
Source dataset
uspto-grants-2016_06
Patent number
US09371336B2

Reaction notes

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