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

Temperature

0 °C

A solution of 1-allyl-3-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionyl]-urea (prepared in Example 24, 765 mg, 2.07 mmol) in tetrahydrofuran (50 mL) cooled to 0° C. was treated with a 1.0M borane solution in tetrahydrofuran (4.14 mL, 4.14 mmol). The reaction was allowed to warm from 0° C. to 25° C. over 1 h. At this time, the reaction was re-cooled to 0° C. and treated with ethanol (15 mL) followed by a mixture of a saturated aqueous sodium bicarbonate solution (45 mL) and hydrogen peroxide (15 mL). The resulting mixture was allowed to warm from 0° C. to 25° C. over 1 h. The reaction was then slowly quenched with a saturated aqueous sodium sulfite solution and then extracted with ethyl acetate (3×30 mL). The organics were washed with a saturated aqueous sodium chloride solution (1×20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded 1-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionyl]-3-(2-hydroxy-propyl)-urea (103 mg, 11%) as a white foam: [α]23589=−33.0° (c=0.094, chloroform); EI-HRMS m/e calcd for C18H24Cl2N2O3 (M+) 386.1164, found 386.1151.

1. temperatureto warm from 0° C. to 25° C. over 1 h
2. temperatureto warm from 0° C. to 25° C. over 1 h
3. customThe reaction was then slowly quenched with a saturated aqueous sodium sulfite solution
4. extractionextracted with ethyl acetate (3×30 mL)
5. washThe organics were washed with a saturated aqueous sodium chloride solution (1×20 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-be73a569a1f449e7a3b1dfdad681e1d6

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1