Hydrochloric Acid → 4-{1-[4-Amino-3-(methyloxy)phenyl]-4-piperidinyl}-1-(2-fluoroethyl)-2-piperazinone

HRID 419445Notes

Reaction equation

HRID 419445 reaction equation
[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[C:18]([O:25][CH3:26])[CH:17]=3)[CH2:12][CH2:11]2)[CH2:6][C:5]1=[O:27].[Sn](Cl)Cl.Cl>O1CCOCC1>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([N:13]2[CH2:12][CH2:11][CH:10]([N:7]3[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][F:1])[C:5](=[O:27])[CH2:6]3)[CH2:15][CH2:14]2)=[CH:17][C:18]=1[O:25][CH3:26]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24479Stannous ChlorideHCID 594526081-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone

Product 1

HCID 594527794-{1-[4-Amino-3-(methyloxy)phenyl]-4-piperidinyl}-1-(2-fluoroethyl)-2-piperazinoneYield 91%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

1-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone (0.832 g, 2.19 mmol) was dissolved in 50 mL of dioxane with stirring and cooled to 0° C. Tin(II) chloride (1.66 g, 8.76 mmol) in concentrated HCl (37%, 15.0 mL, 167 mmol) was added dropwise via pipet. The reaction was warmed to rt and stirred overnight. The reaction was quenched by the slow addition of 6N NaOH solution until the pH was greater than 10. The mixture was extracted with EtOAc, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.695 g (91%) of the title compound of step C. 1H NMR (400 MHz, DMSO-d6) δ 6.50-6.40 (m, 2H), 6.25 (dd, J=8.4, 2.0 Hz, 1H), 4.56 (t, J=4.9 Hz, 1H), 4.44 (t, J=4.9 Hz, 1H), 4.15 (br. s., 2H), 3.69 (s, 3H), 3.58 (t, J=4.9 Hz, 1H), 3.52 (t, J=4.9 Hz, 1H), 3.44-3.33 (m, 2H), 3.32-3.23 (m, 2H), 3.10 (s, 2H), 2.69 (t, J=5.4 Hz, 2H), 2.52-2.39 (m, 2H), 2.32-2.20 (m, 1H), 1.74-1.86 (m, 2H), 1.39-1.55 (m, 2H).

Workup

  1. temperatureThe reaction was warmed to rt
  2. stirringstirred overnight
  3. customThe reaction was quenched by the slow addition of 6N NaOH solution until the pH was greater than 10
  4. extractionThe mixture was extracted with EtOAc
  5. washthe organic layer was washed with brine
  6. extractionThe combined aqueous layers were extracted with EtOAc
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-f7a3490ae8554f7f8d58c8356705ae31
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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