Potassium Hydroxide → (2RS,5RS)-3-{3-[2-(2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acid

HRID 975941Notes

Reaction equation

HRID 975941 reaction equation
[OH-].[K+].C([O:5][C:6]([C:8]1[CH:9]=[C:10]([NH:14][C:15](=[O:38])[NH:16][CH2:17][C:18]([N:20]2[CH:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:30][CH2:29][CH:21]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:19])[CH:11]=[CH:12][CH:13]=1)=[O:7])C>O.CO>[C:25]([O:24][C:22]([CH:21]1[CH2:29][CH2:30][CH:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:20]1[C:18](=[O:19])[CH2:17][NH:16][C:15](=[O:38])[NH:14][C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=1)[C:6]([OH:7])=[O:5])=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 76492990tert-butyl (2RS,5SR)-1-{2-[3-(3-ethoxycarbonylphenyl)ureido]acetyl}-5-phenylprolinate

Product 1

HCID 22125672(2RS,5RS)-3-{3-[2-(2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acidYield 59.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

0.9 g of potassium hydroxide dissolved in 60 cm3 of distilled water is added to a solution of 8 g of tert-butyl (2RS,5SR)-1-{2-[3-(3-ethoxycarbonylphenyl)ureido]acetyl}-5-phenylprolinate in 120 cm3 of methanol. The reaction mixture is stirred for 3 hours at a temperature in the vicinity of 25° C. then concentrated to 50 cm3 under reduced pressure. The solution obtained is diluted with 30 cm3 of water, washed with 2 times 50 cm3 of ethyl acetate, acidified to a pH of 2 with a 4N aqueous hydrochloric acid solution and extracted with 3 times 100 cm3 of dichloromethane. The organic phases are combined, washed with 2 times 50 cm3 of water, dried over magnesium sulphate and concentrated to dryness under reduced pressure at a temperature in the vicinity of 40° C. The crude product obtained is purified by chromatography on silica [eluent: dichloromethane/methanol (90/10 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure. After recrystallization in ethyl acetate, 4.5 g of (2RS,5SR)-3-{3-[2-(2-tert-butyoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acid, melting at 236° C., are obtained.

Workup

  1. concentrationthen concentrated to 50 cm3 under reduced pressure
  2. customThe solution obtained
  3. washwashed with 2 times 50 cm3 of ethyl acetate
  4. extractionextracted with 3 times 100 cm3 of dichloromethane
  5. washwashed with 2 times 50 cm3 of water
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated to dryness under reduced pressure at a temperature in the vicinity of 40° C
  8. customThe crude product obtained
  9. customis purified by chromatography on silica [eluent: dichloromethane/methanol (90/10 by volume)]
  10. additionThe fractions containing the expected product
  11. concentrationconcentrated to dryness under reduced pressure
  12. customAfter recrystallization in ethyl acetate

Sources & evidence

ORD record
ord-b57239975d3242fc8ee331c6f7bc941e
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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