Thionyl Chloride → HCID 19001988, compound

HRID 2259957Notes

Reaction equation

HRID 2259957 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:19][C:20]1[CH:21]=[C:22]([NH:26][C:27](=[O:33])[NH:28][CH2:29][C:30](O)=[O:31])[CH:23]=[CH:24][CH:25]=1.S(Cl)(Cl)=O.C(=O)([O-])O.[Na+]>ClCCCl.O>[CH3:19][C:20]1[CH:21]=[C:22]([NH:26][C:27](=[O:33])[NH:28][CH2:29][C:30]([N:10]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)=[O:31])[CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 149969602-{[(3-Methylphenyl)carbamoyl]amino}acetic acidHCID 22989696HCID 22989696, compound

Product 1

HCID 19001988HCID 19001988, compoundYield 36.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

tert-Butyl 2-[(4-nitrophenyl)amino]acetate (4.5 g) is added at a temperature in the region of 20° C. to a suspension, maintained under an argon atmosphere, of 2-[3-(3-methylphenyl)ureido]acetic acid (3.7 g) in 1,2-dichloroethane (230 cc). The reaction mixture is heated with stirring to reflux of the solvent. Sulphinyl chloride (2.12 g) is then added dropwise while refluxing is maintained. When the addition is complete, heating to reflux is continued for 10 minutes and the reaction mixture is then cooled to a temperature in the region of 10° C. and poured into a solution of sodium hydrogen carbonate (15 g) in water (300 cc). The aqueous phase is separated after settling has taken place and re-extracted with 1,2-dichloroethane (2×50 cc). The organic phases are combined, washed with water (3×20 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The residue is purified by chromatography on silica (0.063-0.2 mm) (200 g) contained in a column 3.5 cm in diameter [eluent: cyclohexane/ethyl acetate (50:50 by volume)], collecting 30-cc fractions. Fractions 16-25 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallisation in ethyl acetate, tert-butyl 2-{2-[3-(3-methylphenyl)ureido]-N-(4-nitrophenyl)acetamido}acetate (2.9 g), m.p. 152° C., is obtained.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux of the solvent
  3. temperaturewhile refluxing
  4. temperatureis maintained
  5. additionWhen the addition
  6. temperatureheating
  7. temperatureto reflux
  8. customThe aqueous phase is separated after settling
  9. extractionre-extracted with 1,2-dichloroethane (2×50 cc)
  10. washwashed with water (3×20 cc)
  11. dry with materialdried over magnesium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  14. customThe residue is purified by chromatography on silica (0.063-0.2 mm) (200 g)
  15. customcollecting 30-cc fractions
  16. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  17. customAfter recrystallisation in ethyl acetate

Sources & evidence

ORD record
ord-cf35b00e54824f449a789a0e4563a063
Source dataset
uspto-grants-1995_12
Patent number
US05475106

Reaction notes

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