Tetrahydrofuran → 1-(2-Fluoroethyl)-4-(6-nitropyridin-3-yl)piperazine

HRID 1919011Notes

Reaction equation

HRID 1919011 reaction equation
[N+:1]([C:4]1[N:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[CH2:17][CH2:18][F:19].C(=O)([O-])[O-].[K+].[K+].C1COCC1>C(Cl)Cl.CO.O.CN(C=O)C>[F:19][CH2:18][CH2:17][N:13]1[CH2:12][CH2:11][N:10]([C:7]2[CH:8]=[N:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 129822-Fluoroethyl bromideHCID 111718041-(6-Nitropyridin-3-yl)piperazine

Product 1

HCID 580442081-(2-Fluoroethyl)-4-(6-nitropyridin-3-yl)piperazineYield 63%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
85 °C

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer, reflux condenser, and nitrogen inlet was charged with 217a (598 mg, 2.87 mmol), 1-bromo-2-fluoroethane (1.09 g, 8.61 mmol), potassium carbonate (1.19 g, 8.61 mmol), THF (10 mL) and DMF (10 mL). The reaction mixture was heated at 85° C. for 14 h under nitrogen atmosphere. After this time, the mixture was diluted with 90:10 methylene chloride/methanol (100 mL) and water (75 mL), and the layers were separated. The aqueous layer was extracted with 90:10 methylene chloride/methanol (50 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, 95:5 methylene chloride/methanol) to afford 217b in 63% yield (460 mg) as a yellow semi-solid: 1H NMR (500 MHz, CDCl3) d 8.16 (d, J=9.0 Hz, 1H), 8.14 (d, J=3.0 Hz, 1H), 7.21 (dd, J=9.0, 2.0 Hz, 1H), 4.67 (t, J=5.0 Hz, 1H), 4.57 (t, J=5.0 Hz, 1H), 3.49 (t, J=5.0 Hz, 4H), 2.81 (t, J=5.0 Hz, 1H), 2.75 (t, J=5.0 Hz, 1H), 2.73 (t, J=5.5 Hz, 4H); MS (ESI+) m/z 255.1 (M+H).

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser, and nitrogen inlet
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with 90:10 methylene chloride/methanol (50 mL)
  5. washthe combined organic layers were washed with brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe drying agent was removed by filtration
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe resulting residue was purified by flash column chromatography (silica, 95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-b0aab9c5c0cb43fda61dc1da4029ed3a
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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