Hydrogen Peroxide → 1-[3-Cyclopentyl-2-(3,4-dichloro-phenyl)-propionyl]-3-(2-hydroxy-propyl)-urea

HRID 1860158Notes

Reaction equation

HRID 1860158 reaction equation
[CH2:1]([NH:4][C:5]([NH:7][C:8](=[O:24])[CH:9]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=1)[CH2:10][CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:6])[CH:2]=[CH2:3].B.[O:26]1CCCC1.C(=O)(O)[O-].[Na+].OO>O1CCCC1.C(O)C>[CH:11]1([CH2:10][CH:9]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[C:8]([NH:7][C:5]([NH:4][CH2:1][CH:2]([OH:26])[CH3:3])=[O:6])=[O:24])[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 516892Sodium BicarbonateHCID 2723981Borane;tetrahydrofuranHCID 186266071-Allyl-3-[3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionyl]-urea

Product 1

HCID 186266211-[3-Cyclopentyl-2-(3,4-dichloro-phenyl)-propionyl]-3-(2-hydroxy-propyl)-ureaYield 26%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-allyl-3-[3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionyl]-urea (prepared in Example 12B-e, 132 mg, 0.36 mmol) in tetrahydrofuran (10 mL) cooled to 0° C. was treated with a 1M solution of borane-tetrahydrofuran (0.7 mL, 0.72 mmol). The reaction mixture was allowed to warm from 0° C. to 25° C. over 1 h. At this time, the solution was re-cooled to 0° C. and treated with ethanol (2 mL) followed by the slow addition of a mixture of a saturated aqueous sodium bicarbonate solution (6 mL) and 30% hydrogen peroxide (2 mL). The resulting mixture was allowed to slowly warm to 25° C. over 1 h. At this time, the reaction was re-cooled to 0° C. and was slowly quenched with a saturated aqueous sodium sulfite solution (20 mL). This mixture was extracted with ethyl acetate (3×20 mL). The organics were washed with a saturated aqueous sodium chloride solution (1×15 mL), dried over sodium sulfate, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexaneslethyl acetate) effected the separation of two spots, the first of the two product spots to elute off the column afforded 1-[3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionyl]-3-(2-hydroxy-propyl)-urea (36 mg, 26%) as a white solid: mp 116.7-119.9° C.; EI-HRMS m/e calcd for C18H24Cl2N2O3 (M+) 386.1164, found 386.1173.

Workup

  1. temperatureto warm from 0° C. to 25° C. over 1 h
  2. temperatureto slowly warm to 25° C. over 1 h
  3. temperatureAt this time, the reaction was re-cooled to 0° C.
  4. customwas slowly quenched with a saturated aqueous sodium sulfite solution (20 mL)
  5. extractionThis mixture was extracted with ethyl acetate (3×20 mL)
  6. washThe organics were washed with a saturated aqueous sodium chloride solution (1×15 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customthe separation of two spots
  10. washthe first of the two product spots to elute off the column

Sources & evidence

ORD record
ord-402ee6aa772f4d418bdeb7a1811f0681
Source dataset
uspto-grants-2003_03
Patent number
US06528543B1

Reaction notes

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