Acetic Acid → 1-{1-[3-(Ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine

HRID 419632Notes

Reaction equation

HRID 419632 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([N:27]2[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]2)[CH:21]=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25])[CH3:16].[CH3:34][S:35]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)(=[O:37])=[O:36].C(O)(=O)C.C([O-])(O)=O.[Na+]>ClCCCl>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([N:27]2[CH2:32][CH2:31][CH:30]([N:41]3[CH2:42][CH2:43][N:38]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:39][CH2:40]3)[CH2:29][CH2:28]2)[CH:21]=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25])[CH3:16]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 598602691-[3-(Ethyloxy)-4-nitrophenyl]-4-piperidinone

Product 1

HCID 594527701-{1-[3-(Ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazineYield 45%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodiumtriacetoxyborohydride (2.59 g, 12.2 mmol) was added to a stirring suspension of 1-[3-(ethyloxy)-4-nitrophenyl]-4-piperidinone (2.15 g, 8.14 mmol), 1-(methylsulfonyl)piperazine (2.67 g, 16.3 mmol), acetic acid (0.70 mL, 12.2 mmol), and TEA (1.13 mL, 8.14 mmol) in 1,2-DCE (100 mL). The reaction was stirred at rt overnight then poured into saturated NaHCO3 (aq). The layers were separated and the aqueous layer was extracted with DCM. The combined organic layers were then dried, filtered and concentrated in vacuo. The residue was purified by flash chromatography to afford 1-{1-[3-(ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine (1.50 g, 45%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.86 (d, J=9.4 Hz, 1H), 6.58 (dd, J=9.5, 2.4 Hz, 1H), 6.50 (d, J=2.5 Hz, 1H), 4.18 (q, J=7.0 Hz, 2H), 3.99-4.08 (m, 2H), 3.04-3.12 (m, 4H), 2.90-2.99 (m, 2H), 2.86 (s, 3H), 2.55-2.61 (m, 4H), 1.77-1.88 (m, 2H), 1.39-1.50 (m, 2H), 1.35 (t, J=6.9 Hz, 3H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with DCM
  3. customThe combined organic layers were then dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-15236fe0f9c84245b4f57409f578489a
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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