Citric Acid → HCID 23570950, compound

HRID 1823927Notes

Reaction equation

HRID 1823927 reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH:4]([C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([Cl:16])[CH:10]=1)[CH2:5]C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:25])C=CC=CC=1.C([N:37]([CH2:40]C)CC)C.N#N.C(O)(=O)[CH2:45][C:46]([CH2:51]C(O)=O)([C:48](O)=O)[OH:47]>C1(C)C=CC=CC=1.[Sn](Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:17])[CH:4]([C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([Cl:16])[CH:10]=1)[CH2:5][NH:37][C:40]([O:47][C:46]([CH3:45])([CH3:48])[CH3:51])=[O:25]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 947NitrogenHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 15524254HCID 15524254, compound

Product 1

HCID 23570950HCID 23570950, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 24287Tin tetrachlorideCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-(3,4-dichloro-phenyl)-succinic acid 1-methyl ester (0.071 mol) in toluene (200 ml) at 0° C. were successively added diphenylphosphoryl azide (16.82 ml, 0.078 mol) and triethylamine (14.83 ml, 0.106 mol). The mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with 1% citric acid (100 ml) and extracted with EtOAc (3×150 ml). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting oil was dissolved in tert-butanol (200 ml). Tin(IV) chloride (0.5 ml, 0.004 mol) was added and the mixture was heated to 80° C. for 1 hour (N2 evolving). The reaction mixture was cooled down to room temperature, quenched with a saturated solution of NaHCO3. Tert-Butanol was removed in vacuo and the mixture was extracted with EtOAc (3×150 ml). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by silica gel column chromatography using as eluent petrol: EtOAc (9:1) to give the title compound (17.35 g) in 70% yield.). 1H NMR (400 MHz, DMSO-d6) δ 1.31 (9H, s), 3.25–3.40 (1H, m), 3.41–3.52 (1H, m), 3.61 (3H, s), 3.90 (1H, t), 6.95 (1H, t), 7.26 (1H, m); 7.52 (1H, s), 7.60 (1H, d); MS (ES+): m/e 348.2 (7%); MS (ES−): m/e=457.2 (100%), 459.2 (70%), 461.2 (15%).

Workup

  1. customat 0° C.
  2. extractionextracted with EtOAc (3×150 ml)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting oil was dissolved in tert-butanol (200 ml)
  7. temperatureThe reaction mixture was cooled down to room temperature
  8. customquenched with a saturated solution of NaHCO3
  9. customTert-Butanol was removed in vacuo
  10. extractionthe mixture was extracted with EtOAc (3×150 ml)
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customThe crude mixture was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6fa5c41a9cb9401da830cb9e090170fb
Source dataset
uspto-grants-2006_05
Patent number
US07041687B2

Reaction notes

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