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

HRID 1160420Notes

Reaction equation

HRID 1160420 reaction equation
B.C1C[O:5]CC1.[Cl:7][C:8]1[CH:15]=[C:14]([N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[C@H:17]2[CH2:21][C:20](=[O:22])[N:19]([CH2:23][CH:24]=[CH2:25])[CH2:18]2)[CH:13]=[CH:12][C:9]=1[C:10]#[N:11].O.OO.[OH-].[Na+]>C1COCC1>[Cl:7][C:8]1[CH:15]=[C:14]([N:16]([C@H:17]2[CH2:21][C:20](=[O:22])[N:19]([CH2:23][CH2:24][CH2:25][OH:5])[CH2:18]2)[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[CH:13]=[CH:12][C:9]=1[C:10]#[N:11]

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 962WaterHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 595161582-Chloro-4-{[(2-methylphenyl)methyl][(3S)-5-oxo-1-(2-propen-1-yl)-3-pyrrolidinyl]amino}benzonitrile

Product 1

HCID 595161712-chloro-4-{[(3S)-1-(3-hydroxypropyl)-5-oxo-3-pyrrolidinyl][(2-methylphenyl)methyl]amino}benzonitrileYield 15.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-28ad3df4b40e4256b4466595c7094931
Source dataset
uspto-grants-2010_10
Patent number
US07816395B2

Reaction notes

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