Hydrogen Peroxide → 2-chloro-4-{[(3S)-1-(3-hydroxypropyl)-5-oxo-3-pyrrolidinyl][(2-methylphenyl)methyl]amino}benzonitrile

Borane-THF (1.0 M, 0.25 mL, 0.25 mmol) was added to a solution of 2-chloro-4-{[(2-methylphenyl)methyl][(3S)-5-oxo-1-(2-propen-1-yl)-3-pyrrolidinyl]amino}benzonitrile (20.0 mg, 0.05 mmol), and the reaction mixture stirred at room temperature overnight. Upon complete consumption of the starting material; the reaction mixture was diluted with THF (5 mL), and H2O (1.0 mL, 2.6 mmol) was added dropwise at 0° C. The mixture then warmed to room temperature over 30 min. Hydrogen peroxide (30 wt % in H2O, 36.2 mg, 0.32 mmol) and 2 N NaOH (0.06 mL, 0.12 mmol) were added at 0° C., and the resulting mixture stirred at 25° C. for 1 h and at 60° C. for 2 h. The reaction mixture was cooled and extracted twice with EtOAc. The combined organic extracts were dried over Na2SO4 and concentrated to give a crude mixture of the desired terminal alcohol and secondary alcohol racemate. The title compound (3.0 mg, 14% yield) was isolated as a white solid by HPLC purification: 30×100 Xterra Prep, eluting with water (solvent A) and acetonitrile (solvent B), no TFA; 40 to 100% (solvent B) over 17 min at a flow rate of 30 mL/min. LC-MS (ES) m/e 398.7 (M+H)+.

1. customUpon complete consumption of the starting material
2. additionwas added dropwise at 0° C
3. temperatureThe mixture then warmed to room temperature over 30 min
4. stirringthe resulting mixture stirred at 25° C. for 1 h and at 60° C. for 2 h
5. temperatureThe reaction mixture was cooled
6. extractionextracted twice with EtOAc
7. dry with materialThe combined organic extracts were dried over Na2SO4
8. concentrationconcentrated
9. customto give a crude

ORD 기록

ord-28ad3df4b40e4256b4466595c7094931

출처 데이터셋

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07816395B2