2-Fluoroethyl bromide → tert-Butyl 4-(2-fluoroethyl)piperazine-1-carboxylate

HRID 2427468Notes

Reaction equation

HRID 2427468 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[CH2:15][CH2:16][F:17].C(N(CC)C(C)C)(C)C>C(#N)C>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([CH2:15][CH2:16][F:17])[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 129822-Fluoroethyl bromideHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 21082715tert-Butyl 4-(2-fluoroethyl)piperazine-1-carboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Heat a mixture of 1-boc-piperazine (4.08 g, 21.9 mmol), 1-bromo-2-fluoroethane (16.68 g, 0.131 mol) and N,N-diisopropyl ethyl amine (17.0 g, 0.131 mol) in acetonitrile (40 mL) to 50° C. for 16 hours and then heat to reflux for 7 additional hours. Cool the reaction to room temperature and remove the solvent in vacuo. Treat the residue with 1 N NaOH (25 mL) and extract twice with ethyl acetate. Dry the organic layer with Na2SO4 and purify the crude product on silica with a 0 to 10% Methanol in CH2Cl2 gradient to afford 5.01 g (99%) of 4-(2-fluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl ester (Rf 0.36 (9/1 CH2Cl2/Methanol, I2 stain).

Workup

  1. temperatureHeat
  2. temperatureheat
  3. temperatureto reflux for 7 additional hours
  4. temperatureCool
  5. customthe reaction to room temperature
  6. customremove the solvent in vacuo
  7. additionTreat the residue with 1 N NaOH (25 mL)
  8. extractionextract twice with ethyl acetate
  9. dry with materialDry the organic layer with Na2SO4
  10. custompurify the crude product on silica with a 0 to 10% Methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-3bd8e213ed2043c7874ba4601a16d64f
Source dataset
uspto-grants-2011_06
Patent number
US07968585B2

Reaction notes

Loading…