Methyl vinyl sulfone → 1-[3-(Ethyloxy)-4-nitrophenyl]-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-piperazine

HRID 419401Notes

Reaction equation

HRID 419401 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:13]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH3:2].[CH:25]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH2:26]>O1CCOCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:13]2[CH2:14][CH2:15][N:16]([CH:19]3[CH2:24][CH2:23][N:22]([CH2:26][CH2:25][S:27]([CH3:30])(=[O:29])=[O:28])[CH2:21][CH2:20]3)[CH2:17][CH2:18]2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH3:2]

Participants

4

Reactant 2

HCID 19354Methyl vinyl sulfoneHCID 594528881-[3-(Ethyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazine

Product 1

HCID 666496531-[3-(Ethyloxy)-4-nitrophenyl]-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-piperazineYield 74%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 1-[3-(ethyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazine (Example 91, step A) (0.30 g, 0.90 mmol) and methyl vinyl sulfone (0.29 g, 2.7 mmol) in dioxane (9.0 mL) was stirred under N2. The reaction was heated to 95° C. and stirred for approximately 3 h, then cooled to rt. The reaction mixture was concentrated under vacuum. The residue was taken up in DCM and aqueous (saturated) NaHCO3. The aqueous layer was extracted with DCM (3×). The combined organic layers were dried over MgSO4 and concentrated under vacuum. The residue was chromatographed on silica gel to give the title compound of step A (294 mg, 0.66 mmol, 74%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, 1H, J=9.35 Hz), 6.56 (dd, 1H, J=9.44 and 2.29 Hz), 6.49 (d, 1H, J=2.38 Hz), 4.17 (q, 2H, J=6.96 Hz), 3.36-3.41 (m, 4H), 3.25 (t, 2H, J=6.78 Hz), 3.01 (s, 3H), 2.92 (M, 2H), 2.66 (t, 2H, J=6.78 Hz), 2.57 (m, 4H), 2.15-2.25 (m, 1H), 1.89-1.97 (m, 2H), 1.75 (m, 2H), 1.32-1.40 (m, 5H).

Workup

  1. stirringstirred for approximately 3 h
  2. temperaturecooled to rt
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. extractionThe aqueous layer was extracted with DCM (3×)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated under vacuum
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-f7cec228d4dc451893c59d7398f5311d
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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