(Diethylamino)sulfur trifluoride → 1,4-Dibenzyl-2-(fluoromethyl)piperazine

HRID 1475401Notes

Reaction equation

HRID 1475401 reaction equation
C(N(S(F)(F)[F:7])CC)C.[CH2:10]([N:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][CH:18]1[CH2:30]O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:10]([N:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][CH:18]1[CH2:30][F:7])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 10827800(1,4-Dibenzylpiperazin-2-yl)methanol

Product 1

HCID 144794991,4-Dibenzyl-2-(fluoromethyl)piperazineYield 34.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diethylaminosulfur trifluoride (0.89 g, 5.53 mmol) in DCM (4 mL) at −78° C. under nitrogen was added a solution of (1,4-dibenzyl-piperazin-2-yl)-methanol (1.364 g, 4.61 mmol) in DCM (6 mL), dropwise over 0.2 h (internal temperature <−65° C.). Resulting solution was stirred at −78° C. for 1 h then warmed slowly to 20° C. and stirred thus for 16 h. The mixture was cooled in an ice-methanol bath then ice was added with stirring. The mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with DCM (3×30 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-25% diethyl ether in 40-60 petroleum ether) gave the title compound (0.471 g) as an oil. 1H NMR (CDCl3): 7.38-7.23 (10H, m), 4.93-4.64 (1H, m), 4.55 (1H, ddd), 4.03 (1H, d), 3.52 (3H, d), 2.91 (1H, d), 2.84-2.64 (2H, m), 2.56 (1H, s), 2.48-2.21 (3H, m).

Workup

  1. temperaturethen warmed slowly to 20° C.
  2. stirringstirred thus for 16 h
  3. temperatureThe mixture was cooled in an ice-methanol bath
  4. additionice was added
  5. stirringwith stirring
  6. extractionextracted with DCM (3×30 mL)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. customevaporated in vacuo
  9. customto give an oil
  10. washChromatography (SiO2; gradient elution with 0-25% diethyl ether in 40-60 petroleum ether)

Sources & evidence

ORD record
ord-d230423f79164ee9b5e110ec954abff7
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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