tert-Butyl piperazine-1-carboxylate → HCID 178452235, compound

HRID 2206320Notes

Reaction equation

HRID 2206320 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[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>[OH:8][C:4]1[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]=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 1785160256-chloropyridin-2-ol

Product 1

HCID 178452235HCID 178452235, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
140 °C

Procedure

To 2-chloro-6-hydroxypyridine (12.3 g, 94 mmol) in n-BuOH (50 mL) was added t-butyl piperazine-1-carboxylate (46.0 g, 235 mmol). The mixture was heated at 140° C. for 3 days. The reaction mixture was extracted with ethyl acetate (1.5 L) and washed with saturated NH4Cl solution and then brine. The organic layer was separated, dried over MgSO4, and concentrated under reduced pressure. The resulting solid was dissolved by CH3CN (100 mL) and precipitated by adding water (1 L). The precipitate was filtered, washed with water and ether. The organic layer of the filtrate was separated and concentrated under reduced pressure. The residue was purified by column chromatography (50%-100% EtOAc/hexanes). A total of 18.7 g (71%) of t-butyl 4-(6-hydroxypyridin-2-yl)piperazine-1-carboxylate was obtained as a white solid. MS m/z 280.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.40 (1H, m), 6.04 (1H, d, J=8.8 Hz), 5.64 (1H, d, J=7.2 Hz), 3.62 (4H, m), 3.36 (4H, m), 1.51 (9H, s).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (1.5 L)
  2. washwashed with saturated NH4Cl solution
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting solid was dissolved by CH3CN (100 mL)
  7. customprecipitated
  8. additionby adding water (1 L)
  9. filtrationThe precipitate was filtered
  10. washwashed with water and ether
  11. customThe organic layer of the filtrate was separated
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by column chromatography (50%-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f8624d8fe3d0497ba2cc5f0f400b0c71
Source dataset
uspto-grants-2016_06
Patent number
US09371336B2

Reaction notes

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