Formaldehyde → 4-Methyl-3-(4-nitrophenyl)piperazine-2-one

HRID 1772090Notes

Reaction equation

HRID 1772090 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11](=[O:16])[NH:12][CH2:13][CH2:14][N:15]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C=O.O.[C:20]([BH3-])#N.[Na+].[OH-].[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH3:20][N:15]1[CH2:14][CH2:13][NH:12][C:11](=[O:16])[CH:10]1[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 962WaterHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 57625103HCID 57625103, compound

Product 1

HCID 666098864-Methyl-3-(4-nitrophenyl)piperazine-2-oneYield 100%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

A 10-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen, charged with 104a (196 mg, 0.89 mmol), 37% solution of formaldehyde in water (35 mg, 1.16 mmol) and anhydrous methanol (3 mL). A solution of sodium cyanoborohydride (169 mg, 2.68 mmol) and anhydrous zinc chloride (183 mg, 1.34 mmol) in anhydrous methanol (3 mL) was added, and the reaction was stirred at room temperature for 1 h. After this time, 1N aqueous sodium hydroxide (2 mL) was added, and the methanol was evaporated under reduced pressure. The remaining aqueous solution was extracted with ethyl acetate (3×25 mL). The organic layers were combined, washed with water (20 mL) and brine (20 mL) and dried over magnesium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure to afford 104b in 100% yield (210 mg) as a yellow solid: mp 185-186° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.18 (d, 2H, J=8.1 Hz), 8.05 (d, 1H, J=3.6 Hz), 7.63 (d, 2H, J=7.8 Hz), 3.82 (s, 1H), 3.45 (m, 1H), 3.17 (m, 1H), 2.95 (m, 1H), 2.56 (m, 1H), 2.06 (s, 3H); MS (ESI+) m/z 236 (M+H).

Workup

  1. customA 10-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. customthe methanol was evaporated under reduced pressure
  4. extractionThe remaining aqueous solution was extracted with ethyl acetate (3×25 mL)
  5. washwashed with water (20 mL) and brine (20 mL)
  6. dry with materialdried over magnesium sulfate
  7. customThe drying agent was removed by filtration
  8. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-deefc191e6d5456da08f9a77fd254cde
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

Loading…