Oxalyl chloride → 1-(3-Methoxy-4-nitrophenyl)piperidin-4-one

HRID 419358Notes

Reaction equation

HRID 419358 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9]1[CH:10]=[C:11]([N:18]2[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]2)[CH:12]=[CH:13][C:14]=1[N+:15]([O-:17])=[O:16]>C(Cl)Cl.CS(C)=O>[CH3:7][O:8][C:9]1[CH:10]=[C:11]([N:18]2[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[CH:12]=[CH:13][C:14]=1[N+:15]([O-:17])=[O:16]

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 259188601-(3-Methoxy-4-nitrophenyl)piperidin-4-ol

Product 1

HCID 259188571-(3-Methoxy-4-nitrophenyl)piperidin-4-oneYield 98.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

Oxalyl chloride (11.9 mL, 23.78 mmol) was dissolved in DCM (200 mL) and cooled to −78° C. DMSO (3.4 mL, 47.58 mmol) in DCM (15 mL) was added to the solution dropwise via an addition funnel. Upon completion of addition, the reaction was allowed to stir 10 min. 1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinol (4.04 g, 15.86 mmol) in DMSO (6 mL) and DCM (15 mL) was added dropwise via addition funnel. Upon completion of addition, the reaction was allowed to stir 15 minutes. TEA (11.0 mL, 79.3 mmol) was then added dropwise via addition funnel. Upon completion of addition, the bath was removed and the reaction was allowed to warm to rt. The reaction was stirred until alcohol was consumed as indicated by TLC. The solvent was removed in vacuo and the residue was taken up in EtOAc. The suspension was washed twice with H2O, followed by brine. The organic layer was dried with MgSO4, filtered and concentrated to provide the title compound of step B (3.91 g, 15.59 mmol, 97%) as a bright yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.47-2.51 (m, 4H), 3.82 (t, J=6.2 Hz, 4H), 3.91 (s, 3H), 6.52 (d, J=2.6 Hz, 1H), 6.61 (dd, J=9.5, 2.6 Hz, 1H), 7.91 (d, J=9.5 Hz, 1H).

Workup

  1. additionUpon completion of addition
  2. additionUpon completion of addition
  3. stirringto stir 15 minutes
  4. additionUpon completion of addition
  5. customthe bath was removed
  6. temperatureto warm to rt
  7. stirringThe reaction was stirred until alcohol
  8. customwas consumed
  9. customThe solvent was removed in vacuo
  10. washThe suspension was washed twice with H2O
  11. dry with materialThe organic layer was dried with MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-3d06461a6c4b427d83cde11c13ecca4b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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