Hydrochloric Acid → (2R,3S)-1-(Phenanthrene-2-carbonyl)-piperazine-2,3-dicarboxylic acid

HRID 895376Notes

Reaction equation

HRID 895376 reaction equation
[C:1]([C:4]1[CH:17]=[CH:16][C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=[CH:7][C:6]=2[CH:5]=1)(O)=[O:2].S(Cl)(Cl)=O.[NH:22]1[CH2:27][CH2:26][NH:25][CH:24]([C:28]([OH:30])=[O:29])[CH:23]1[C:31]([OH:33])=[O:32].[OH-].[Na+].Cl>C1C=CC=CC=1.O1CCOCC1>[CH:5]1[C:6]2[CH:7]=[CH:8][C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:15]=2[CH:16]=[CH:17][C:4]=1[C:1]([N:22]1[CH2:27][CH2:26][NH:25][C@H:24]([C:28]([OH:30])=[O:29])[C@@H:23]1[C:31]([OH:33])=[O:32])=[O:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 2809732,3-Piperazinedicarboxylic acidHCID 13234903Phenanthrene-2-carboxylic acid

Product 1

HCID 11485745(2R,3S)-1-(Phenanthrene-2-carbonyl)-piperazine-2,3-dicarboxylic acidYield 12%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Carboxyphenanthrene (2 g, 0.009 mol) was suspended in dry benzene (50 ml) and heated under reflux in the presence of thionyl chloride (5 ml) for 5 hr. The solvent was removed and the corresponding acid chloride was used without further purification. Piperazine-2,3-dicarboxylic acid (0.508 g, 0.003 mol) was dissolved in a 0.991 M aqueous sodium hydroxide solution (9.4 ml, 0.009 mol), dioxane (10 ml) was added and the solution was cooled to 0° C. A solution of the acid chloride (0.84 g, 0.0035 mol) in dioxane (10 ml) was added to the reaction mixture. The reaction was warmed to room temperature and stirred for 2-3 hr. The reaction mixture was acidified to pH 2-3 with aqueous HCl. The solid was filtered, dissolved in dioxane/ H2O (50:50) and bound to an ion exchange resin (Dowex-AG50 H+ form) chromatography column. It was eluted with dioxane/H2O (50:50) until organic impurities are removed. The column was eluted with 10% aqueous pyridine and the ninhydrin fractions were combined. The solvent was removed and the solid was crystallised from H2O to give a white solid (0.128 g, 12%). m.p.=218.1-221.7 ° C. (dec.); 1H NMR (300 MHz, NaOD/ D2O) 7.7-8.8 (m, 9H, Ar), 5.6 (d, 0.5H, CH—CO2H, JAB=2.6Hz), 4.8 (d, 0.5H, CH—CO2H, JAB=2.6Hz), 4.4 (d, 0.4H, CH—CO2H, JAB=12.0Hz), 3.6 (d, 0.4H, CH—CO2H, JAB=12.0Hz), 2.5-3.8 (m, 4H, N—CH2CH2—NH); Elemental analysis calculated for C21,H18N2O5. 2.3H2O C:60.07, H:5.44, N:6.67. Found C:60.06, H:5.38, N: 6.85. The cis-isomerism was confirmed by COSEY 1H NMR.

Workup

  1. temperatureheated
  2. customThe solvent was removed
  3. customthe corresponding acid chloride was used without further purification
  4. additionwas added
  5. temperatureThe reaction was warmed to room temperature
  6. filtrationThe solid was filtered
  7. dissolutiondissolved in dioxane/ H2O (50:50)
  8. washIt was eluted with dioxane/H2O (50:50) until organic impurities
  9. customare removed
  10. washThe column was eluted with 10% aqueous pyridine
  11. customThe solvent was removed
  12. customthe solid was crystallised from H2O

Sources & evidence

ORD record
ord-93393ff3bbbe4896a5725c5c807de49f
Source dataset
uspto-grants-2005_07
Patent number
US06916816B2

Reaction notes

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