Methanol → 1-{2-(3,4-Dichloro-phenyl)-3-[3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-propionyl}-3-methyl-urea
Reaction equation
CO[C:3](=[O:26])[CH:4]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH:8]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH2:7]1.[CH3:27][NH:28][C:29]([NH2:31])=[O:30].C[O-].[Mg+2].C[O-].CO>>[Cl:25][C:20]1[CH:19]=[C:18]([CH:4]([CH2:5][CH:6]2[CH2:10][CH2:9][CH:8]([O:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[CH2:7]2)[C:3]([NH:31][C:29]([NH:28][CH3:27])=[O:30])=[O:26])[CH:23]=[CH:22][C:21]=1[Cl:24]Participants
5
Reactant 4
Product 1
Conditions
- Temperature
- 100 °C
Procedure
2-(3,4-Dichloro-phenyl)-3-[3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester (1.60 mg, 3.98 mmol) and methylurea (443 mg, 5.98 mmol) in a solution of magnesium methoxide in methanol (7.4 wt. %, 11.4 mL, 7.97 mmol) was heated under reflux at 100° C. for 18 h. The reaction mixture was then concentrated in vacuo and filtered through a plug of celite (100% ethyl acetate as eluent). Flash chromatography (Merck Silica gel 60, 230–400 mesh, 50/50 hexanes/ethyl acetate) afforded 1-{2-(3,4-dichloro-phenyl)-3-[3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-propionyl}-3-methyl-urea (160.6 mg, 9.1%) as a white solid: mp 62–65° C.; FAB-HRMS m/e calcd for C21H28Cl2N2O4 (M+Na)+ 465.1324, found 465.1324.
Workup
- concentrationThe reaction mixture was then concentrated in vacuo
- filtrationfiltered through a plug of celite (100% ethyl acetate as eluent)
Sources & evidence
- ORD record
- ord-7f15e93749db4aa2bc69e986c3ca5d16
- Source dataset
- uspto-grants-2006_09
- Patent number
- US07105671B2
Reaction notes
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