Methanol → HCID 18626631, compound

HRID 1860182Notes

Reaction equation

HRID 1860182 reaction equation
CO[C:3](=[O:22])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F: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.[Cl-].[Na+]>>[CH:6]1([CH2:5][CH:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[C:13]([F:21])[CH:12]=2)[C:3]([NH:27][C:25]([NH:24][CH3:23])=[O:26])=[O:22])[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

6

Reactant 5

HCID 887MethanolHCID 5234Sodium ChlorideHCID 11719MethylureaHCID 164537Methanol, magnesium salt (2:1)HCID 537268193-Cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-propionic acid methyl ester

Product 1

HCID 18626631HCID 18626631, compoundYield 38%

Conditions

Temperature
25 °C

Procedure

3-Cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-propionic acid methyl ester (750 mg, 2.36 mmol) and methyl urea (437 mg, 5.90 mmol) were treated with a solution of magnesium methoxide in methanol (7.4 wt %, 14.5 mL, 7.08 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 15 h. The reaction mixture was allowed to cool to 25° C. and then partitioned between water (75 mL) and ethyl acetate (75 mL). An emulsion formed, and a saturated aqueous sodium chloride solution was added to break down the emulsion. The aqueous layer was further extracted with ethyl acetate (2×75 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a white semi-solid. The semi-solid was treated with a solution of 2/1 hexanes/ethyl acetate, and a white solid formed. The solid was filtered, washed well with hexanes, and dried to afford 1-[3-cyclopentyl-2-(3-fluoro-4-trifluoromethyl-phenyl)-propionyl]-3-methyl-urea (322 mg, 38%) as a white solid: mp 187-189° C.; FAB-HRMS m/e calcd for C17H20F4N2O2 (M+H)+361.1539, found 361.1549.

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 15 h
  5. custompartitioned between water (75 mL) and ethyl acetate (75 mL)
  6. customAn emulsion formed
  7. extractionThe aqueous layer was further extracted with ethyl acetate (2×75 mL)
  8. dry with materialThe combined organic layers were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford a white semi-solid
  12. customa white solid formed
  13. filtrationThe solid was filtered
  14. washwashed well with hexanes
  15. customdried

Sources & evidence

ORD record
ord-b9695b7e550f42b5957c923e872228c9
Source dataset
uspto-grants-2003_03
Patent number
US06528543B1

Reaction notes

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