2-(Ethylsulfonyl)ethanol → 4-[2-(Ethylsulfonyl)ethyl]-1-piperazinecarboxylic acid, phenylmethyl ester

HRID 542837Notes

Reaction equation

HRID 542837 reaction equation
[N:1]1([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[H-].[Na+].[CH2:19]([S:21]([CH2:24][CH2:25]O)(=[O:23])=[O:22])[CH3:20].CC1C=CC(S([O-])(=O)=O)=CC=1>CN(C)C=O>[CH2:19]([S:21]([CH2:24][CH2:25][N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:2][CH2:3]1)(=[O:23])=[O:22])[CH3:20]

Participants

6

Reactant 4

HCID 105492-(Ethylsulfonyl)ethanolHCID 24758Sodium hydrideHCID 85570p-ToluenesulfonateHCID 643495Benzyl piperazine-1-carboxylate

Product 1

HCID 867414274-[2-(Ethylsulfonyl)ethyl]-1-piperazinecarboxylic acid, phenylmethyl esterYield 812.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 6.6 g (0.03 mole) of 1-piperazinecarboxylic acid, phenylmethyl ester in 100 ml of N,N-dimethylformamide was added, in portions, 1.44 g (0.03 mole) of a 50% sodium hydride suspension in mineral oil. The mixture was heated at 50° for 1 hr and allowed to cool slightly. To it was added dropwise a solution of 8.8 g (0.003 mole) of 2-(ethylsulfonyl)ethanol, 4-methylbenzenesulfonate in 30 ml of N,N-dimethylformamide. The mixture was heated at 50° for 1 hr, allowed to cool, concentrated under vacuum to one-half the original volume, allowed to stand for four days and then concentrated to a paste. The paste was diluted with ether and the suspension filtered to remove insoluble salts. The filtrate was concentrated and chromatographed over 250 g of silica gel with 1 l each of the following solutions of methanol in ethyl acetate: 1.5%, 3% and 15%. That portion of the eluent containing the product, Rf(silica--10 % methanol/ethyl acetate)=0.7, was concentrated to dryness under vacuum to afford 8.3 g (81%) of the desired product as an oil. The IR and NMR spectra were consistent with the assigned structure.

Workup

  1. temperatureThe mixture was heated at 50° for 1 hr
  2. temperatureto cool slightly
  3. temperatureThe mixture was heated at 50° for 1 hr
  4. temperatureto cool
  5. concentrationconcentrated under vacuum to one-half the original volume
  6. concentrationconcentrated to a paste
  7. additionThe paste was diluted with ether
  8. filtrationthe suspension filtered
  9. customto remove insoluble salts
  10. concentrationThe filtrate was concentrated
  11. customchromatographed over 250 g of silica gel with 1 l each of the following solutions of methanol in ethyl acetate
  12. additionThat portion of the eluent containing the product, Rf(silica--10 % methanol/ethyl acetate)=0.7
  13. concentrationwas concentrated to dryness under vacuum

Sources & evidence

ORD record
ord-e132cda5cec24a25a613422976e21a23
Source dataset
uspto-grants-1987_04
Patent number
US04659708

Reaction notes

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