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

HRID 419397Notes

Reaction equation

HRID 419397 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH3:2].C([N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1)(OC(C)(C)C)=O.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:13]2[CH2:14][CH2:15][N:16]([CH:29]3[CH2:30][CH2:31][NH:26][CH2:27][CH2:28]3)[CH2:17][CH2:18]2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 594525801-(3-Ethoxy-4-nitrophenyl)piperazine

Product 1

HCID 594528881-[3-(Ethyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazineYield 80%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of 1-[3-(ethyloxy)-4-nitrophenyl]piperazine (Example 143, step A) (0.53 g, 2.1 mmol) and 1-BOC-4-piperidone (2.1 g, 10.6 mmol) in DCE (21 mL) was added HOAc (0.25 g, 4.2 mmol) followed by addition of sodium triacetoxyborohydride (2.2 g, 10.6 mmol). The reaction was stirred under N2 at rt for 3 h. The reaction was quenched with aqueous (saturated) NaHCO3 and extracted with DCM (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. The desired fractions were concentrated under vacuum. The residue was dissolved and stirred in a 20% solution of TFA/DCM (50 mL) for approximately 2 h at rt. The mixture was concentrated under vacuum. The residue was dissolved in DCM and neutralized with aqueous (saturated) NaHCO3. The aqueous layer was extracted with DCM (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. The desired fractions were concentrated under vacuum to give the title compound of step A (560 mg, 1.68 mmol, 79%) as a yellow solid. MS (ESI): 335 [M+H]+.

Workup

  1. customThe reaction was quenched with aqueous (saturated) NaHCO3
  2. extractionextracted with DCM (3×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by silica gel chromatography
  7. concentrationThe desired fractions were concentrated under vacuum
  8. dissolutionThe residue was dissolved
  9. stirringstirred in a 20% solution of TFA/DCM (50 mL) for approximately 2 h at rt
  10. concentrationThe mixture was concentrated under vacuum
  11. dissolutionThe residue was dissolved in DCM and neutralized with aqueous (saturated) NaHCO3
  12. extractionThe aqueous layer was extracted with DCM (3×)
  13. dry with materialThe combined organic layers were dried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated under vacuum
  16. customThe residue was purified by silica gel chromatography
  17. concentrationThe desired fractions were concentrated under vacuum

Sources & evidence

ORD record
ord-b2f184a53dd34503b7e72fcdeef46ded
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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