Sodium hydride → 1-Piperazinecarboxylic acid, 4-(3-hydroxy-2-nitrophenyl)-, 1,1-dimethylethyl ester

HRID 491418Notes

Reaction equation

HRID 491418 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16](F)[C:15]=2[N+:21]([O-:23])=[O:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CS(CCO)(=O)=[O:26].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:26])[C:15]=2[N+:21]([O-:23])=[O:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydride3×HCID 848342-(Methylsulfonyl)ethanolHCID 53255497tert-Butyl 4-(3-fluoro-2-nitrophenyl)piperazine-1-carboxylate

Product 1

HCID 576783021-Piperazinecarboxylic acid, 4-(3-hydroxy-2-nitrophenyl)-, 1,1-dimethylethyl esterYield 148.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a cooled stirring solution of 4-(3-fluoro-2-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1.50 g, 4.61 mmol), and 2-(methylsulfonyl)ethanol (876 mg, 6.92 mmol) in anhydrous DMF (15 mL), under nitrogen, was added, portionwise, sodium hydride (553 mg, 13.8 mmol, 60% oil dispersion). The solution foamed upon the sodium hydride addition. The resulting dark orange solution was stirred, at 0° C., for 30 minutes upon completion of sodium hydride addition. The reaction solution became viscous and additional DMF (5 mL) was added, via syringe, the ice bath removed and the dark solution stirred at room temperature, under nitrogen, for 2 h. The reaction was cooled in an ice bath, quenched with 0.1N hydrochloric acid solution, and transferred to a separatory funnel with ethyl acetate (100 mL). This organic phase was washed with brine (75 mL×3). The aqueous washings were combined and extracted with ethyl acetate (75 mL×3). The organic extracts were combined and washed with saturated aqueous sodium bicarbonate solution (100 mL), brine (100 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed to give an amber colored oil (2.21 g). This oil was adsorbed onto silica and purified by column chromatography, eluting with 50% ethyl acetate in hexane to afford the product as a light yellow colored solid (1.37 g, 92%). Mass Spectrum (+ESI): 324 [M+H]+, 322 [M−H]−.

Workup

  1. additionunder nitrogen, was added
  2. customthe ice bath removed
  3. temperatureThe reaction was cooled in an ice bath
  4. customquenched with 0.1N hydrochloric acid solution
  5. customtransferred to a separatory funnel with ethyl acetate (100 mL)
  6. washThis organic phase was washed with brine (75 mL×3)
  7. extractionextracted with ethyl acetate (75 mL×3)
  8. washwashed with saturated aqueous sodium bicarbonate solution (100 mL), brine (100 mL)
  9. dry with materialdried with anhydrous sodium sulfate
  10. filtrationfiltered
  11. customthe solvent removed

Sources & evidence

ORD record
ord-0521a74df5d14ae7a35cb3420f611ba3
Source dataset
uspto-grants-2009_05
Patent number
US07531542B2

Reaction notes

Loading…