1-(4-Nitrophenyl)piperazine → 1-(4-Nitrophenyl)-4-(oxetan-3-yl)piperazine

HRID 1024076Notes

Reaction equation

HRID 1024076 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[O:16]1[CH2:19][C:18](=O)[CH2:17]1.[BH3-]C#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH:18]3[CH2:19][O:16][CH2:17]3)[CH2:12][CH2:11]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

6

Reactant 3

HCID 804471-(4-Nitrophenyl)piperazineHCID 5003444Sodium cyanoborohydrideHCID 150242543-Oxetanone

Product 1

HCID 866841521-(4-Nitrophenyl)-4-(oxetan-3-yl)piperazineYield 76.1%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 117c (2.0 g, 8.23 mmol), zinc chloride (2.2 g, 16.4 mmol), oxetan-3-one (1.18 g, 16.4 mmol) in methanol (80 mL) was added NaBH3CN (1.02 g, 16.4 mmol). The mixture was stirred at 50° C. for 5 hours. The mixture was then concentrated under reduced pressure and the residue was diluted with water (100 mL). It was extracted with dichloromethane (3×100 mL) and the combined organic layer was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 4:1 petroleum ether/ethyl acetate to afford 117d (1.65 g, 76%) as a yellow solid. MS: [M+H]+ 264.

Workup

  1. concentrationThe mixture was then concentrated under reduced pressure
  2. additionthe residue was diluted with water (100 mL)
  3. extractionIt was extracted with dichloromethane (3×100 mL)
  4. concentrationthe combined organic layer was concentrated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 4:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-23338a47893f43129b7db68213723005
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

Loading…