Methanol → 1-[3-Cyclopentyl-2-(3-fluoro4-methanesulfonyl-phenyl)-propionyl]-3-methyl-urea

HRID 1860221Notes

Reaction equation

HRID 1860221 reaction equation
CO[C:3](=[O:22])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([F:21])[CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:23][NH:24][C:25]([NH2:27])=[O:26].C[O-].[Mg+2].C[O-].CO>>[CH:6]1([CH2:5][CH:4]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:18])=[O:19])=[C:13]([F:21])[CH:12]=2)[C:3]([NH:27][C:25]([NH:24][CH3:23])=[O:26])=[O:22])[CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

5

Reactant 4

HCID 887MethanolHCID 11719MethylureaHCID 164537Methanol, magnesium salt (2:1)HCID 536938863-Cyclopentyl-2-(3-fluoro-4-methanesulfonyl-phenyl)-propionic acid methyl ester

Product 1

HCID 186266521-[3-Cyclopentyl-2-(3-fluoro4-methanesulfonyl-phenyl)-propionyl]-3-methyl-ureaYield 23%

Conditions

Temperature
25 °C

Procedure

3-Cyclopentyl-2-(3-fluoro-4-methanesulfonyl-phenyl)-propionic acid methyl ester (90 mg, 0.274 mmol) and methyl urea (61 mg, 0.822 mmol) were treated with a solution of magnesium methoxide in methanol (7.4 wt %, 1.0 mL, 0.685 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 24 h. The resulting cloudy, white reaction mixture was allowed to cool to 25° C. and then filtered through celite. The celite was thoroughly washed with ethyl acetate. The filtrate was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded 1-[3-cyclopentyl-2-(3-fluoro4-methanesulfonyl-phenyl)-propionyl]-3-methyl-urea (23.3 mg, 23%) as a white solid: mp 199-200° C.; EI-HRMS m/e calcd for C17H23FN2O4S (M+) 370.1362, found 370.1370.

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 24 h
  5. filtrationfiltered through celite
  6. washThe celite was thoroughly washed with ethyl acetate
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-c4c4ee1739e240778a1e9b789315d3e9
Source dataset
uspto-grants-2003_03
Patent number
US06528543B1

Reaction notes

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