Thionyl Chloride → tert-butyl (2RS,5SR)-1-{2-[3-(3-methylphenyl)ureido]acetyl}-5-phenylprolinate

HRID 975938Notes

Reaction equation

HRID 975938 reaction equation
S(Cl)(Cl)=O.[C:5]1([CH:11]2[NH:15][CH:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:23][C:24]1[CH:25]=[C:26]([NH:30][C:31](=[O:37])[NH:32][CH2:33][C:34](O)=[O:35])[CH:27]=[CH:28][CH:29]=1.C(=O)(O)[O-].[Na+]>ClCCCl>[CH3:23][C:24]1[CH:25]=[C:26]([NH:30][C:31](=[O:37])[NH:32][CH2:33][C:34]([N:15]2[CH:11]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH2:12][CH2:13][CH:14]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:35])[CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 149969602-{[(3-Methylphenyl)carbamoyl]amino}acetic acidHCID 18928042tert-butyl (2RS,5SR)-5-phenylprolinate

Product 1

HCID 44210765tert-butyl (2RS,5SR)-1-{2-[3-(3-methylphenyl)ureido]acetyl}-5-phenylprolinateYield 18.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

0.9 cm3 of sulphinyl chloride is added slowly to a suspension of 3.1 g of tert-butyl (2RS,5SR)-5-phenylprolinate and 2.6 g of 2-[3-(3-methylphenyl)ureido]acetic acid in 100 cm3 of anhydrous 1,2-dichloroethane heated to reflux. The reaction mixture is then heated under reflux for 15 minutes, then cooled to 50° C. and neutralized to a pH of 7-8 by addition of a 10% aqueous sodium bicarbonate solution. The organic phase is washed with 3 times 50 cm3 of water, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure. The crude product obtained is purified by chromatography on silica [eluent: dichloromethane/methanol (98/2 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure at a temperature in the vicinity of 45° C. After recrystallization in acetonitrile, 1 g of tert-butyl (2RS,5SR)-1-{2-[3-(3-methylphenyl)ureido]acetyl}-5-phenylprolinate, melting at 156° C., is obtained.

Workup

  1. temperatureheated to reflux
  2. temperatureThe reaction mixture is then heated
  3. temperatureunder reflux for 15 minutes
  4. washThe organic phase is washed with 3 times 50 cm3 of water
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe crude product obtained
  9. customis purified by chromatography on silica [eluent: dichloromethane/methanol (98/2 by volume)]
  10. additionThe fractions containing the expected product
  11. concentrationconcentrated to dryness under reduced pressure at a temperature in the vicinity of 45° C
  12. customAfter recrystallization in acetonitrile

Sources & evidence

ORD record
ord-1450186293bd4f7fb23ad1b23389890c
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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