Potassium Carbonate → Tert-butyl 4-(6-chloroquinolin-2-yl)piperazine-1-carboxylate

HRID 1772205Notes

Reaction equation

HRID 1772205 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1.[N:13]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:16]1[CH2:15][CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17]1)[CH:11]=[CH:10]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 6075022,6-Dichloroquinoline

Product 1

HCID 58906309Tert-butyl 4-(6-chloroquinolin-2-yl)piperazine-1-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2,6-dichloroquinoline (1.5 g, 7.6 mmol) in DMF (50 ml) was added tert-butyl piperazine-1-carboxylate (7.1 g, 38.1 mmol, 5 eq), and potassium carbonate (2.1 g, 15.1 mmol, 2 eq). The mixture was stirred for 4 hours at 140° C. and then quenched by the addition of water (300 ml) and then extracted with ethyl acetate (3×100 ml). The organic layers were combined, washed with saturated aqueous sodium chloride (3×300 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue. The crude material was purified by silica gel chromatography using 1-10% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford tert-butyl 4-(6-chloroquinolin-2-yl)piperazine-1-carboxylate as a light yellow solid (1.6 g, 61%). (ES, m/z): [M+H]+ 348; 1H NMR (300 MHz, DMSO): δ 8.03 (d, J=9.3 Hz, 1H), 7.81 (d, J=2.1 Hz, 1H), 7.50-7.58 (m, 2H), 7.29 (d, J=9.3 Hz, 1H), 3.68-3.71 (t, J=5.1 Hz, 4H), 3.43-3.47 (t, J=4.5 Hz, 4H), 1.43 (s, 9H).

Workup

  1. customquenched by the addition of water (300 ml)
  2. extractionextracted with ethyl acetate (3×100 ml)
  3. washwashed with saturated aqueous sodium chloride (3×300 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give a residue
  8. customThe crude material was purified by silica gel chromatography
  9. washto elute
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7a87bf027e464c5ca199c7a41a66b7d7
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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