Methanol → 1-[3-Cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionyl]-3-methyl-urea

HRID 1860186Notes

Reaction equation

HRID 1860186 reaction equation
C(O[C:4](=[O:23])[CH:5]([C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH2:21][CH3:22])(=[O:20])=[O:19])=[CH:14][CH:13]=1)[CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)C.[CH3:24][NH:25][C:26]([NH2:28])=[O:27].C[O-].[Mg+2].C[O-].CO>C(OCC)(=O)C>[CH:7]1([CH2:6][CH:5]([C:12]2[CH:13]=[CH:14][C:15]([S:18]([CH2:21][CH3:22])(=[O:19])=[O:20])=[CH:16][CH:17]=2)[C:4]([NH:28][C:26]([NH:25][CH3:24])=[O:27])=[O:23])[CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 887MethanolHCID 11719MethylureaHCID 164537Methanol, magnesium salt (2:1)HCID 543970993-Cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionic acid ethyl ester

Product 1

HCID 186266321-[3-Cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionyl]-3-methyl-ureaYield 33%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

3-Cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionic acid ethyl ester (500 mg, 1.48 mmol) and methyl urea (274 mg, 3.70 mmol) were treated with a solution of magnesium methoxide in methanol (7.4 wt %, 6.5 mL, 4.43 mmol). The reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol. The resulting reaction mixture was then heated under reflux for 2 d. The reaction mixture was allowed to cool to 25° C. and then diluted with ethyl acetate (25 mL). The mixture was filtered through a pad of celite, and the celite pad was washed with ethyl acetate (50 mL). The resulting filtrate was washed with water (40 mL) then the water layer was further extracted with ethyl acetate (40 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a colorless oil. The oil was treated with a solution of 2/1 hexanes/ethyl acetate (10 mL), and a white solid began to precipitate. The suspension was placed in the freezer to enhance crystallization. The solid was filtered to afford 1-[3-cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionyl]-3-methyl-urea (178 mg, 33%) as a white solid: mp 200-201° C.; FAB-HRMS m/e calcd for C18H26N2O4S (M+H)+367.1691, found 367.1697.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol
  2. customThe resulting reaction mixture
  3. temperaturewas then heated
  4. temperatureunder reflux for 2 d
  5. filtrationThe mixture was filtered through a pad of celite
  6. washthe celite pad was washed with ethyl acetate (50 mL)
  7. washThe resulting filtrate was washed with water (40 mL)
  8. extractionthe water layer was further extracted with ethyl acetate (40 mL)
  9. dry with materialThe combined organic layers were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto afford a colorless oil
  13. customto precipitate
  14. customcrystallization
  15. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-50fb0e522a3e4fa08497f28b8a619307
Source dataset
uspto-grants-2003_03
Patent number
US06528543B1

Reaction notes

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