Sodium borohydride → HCID 118277053, compound

HRID 1053705Notes

Reaction equation

HRID 1053705 reaction equation
[BH4-].[Na+].[H][H].[C:5]([C:7]1[CH:8]=[CH:9][C:10]([CH3:23])=[C:11]([CH:13]([CH2:19][N+:20]([O-])=O)[CH2:14][C:15](OC)=[O:16])[CH:12]=1)#[N:6]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[NH2:6][CH2:5][C:7]1[CH:8]=[CH:9][C:10]([CH3:23])=[C:11]([CH:13]2[CH2:19][NH:20][C:15](=[O:16])[CH2:14]2)[CH:12]=1

Participants

6

Reactant 3

HCID 4311764Sodium borohydride2×HCID 118277066HCID 118277066, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 118277053HCID 118277053, compound

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
55 °C

Procedure

Adapting a literature known protocol (Osby and Ganem, Tetrahedron Lett., 1985, 26(52), 6413-6416), a mixture of nickel(II) dichloride hexahydrate (NiCl2 6H2O) (1.19 g, 5.0 mmol) in methanol (MeOH) (80 mL) is sonicated to effect complete dissolution. Solid sodium borohydride (NaBH4) (567 mg, 15.0 mmol) is added in small portions upon a black precipitate (Ni2B) is generated immediately and hydrogen gas is generated (exotherm!). After about 30 min, a solution of methyl 3-(5-cyano-2-methyl-phenyl)-4-nitro-butanoate (22b) (2.62 g, 10.0 mmol) in MeOH (20 mL) is added followed by portion-wise addition of more NaBH4 (1.13 g, 30.0 mmol) at room temperature. The reaction is monitored by TLC and/or LCMS till completion. The reaction mixture is filtered over Celite® 545 and the filter residue is washed with additional MeOH. The combined filtrates are partially evaporated under reduced pressure using a rotary evaporator and the crude material is heated to 50-60° C. to complete the lactamization. Purification by silica gel column chromatography with mixtures of (MeOH) and dichloromethane (DCM) furnishes the title compound 4-[5-(aminomethyl)-2-methyl-phenyl]pyrrolidin-2-one (22c).

Workup

  1. customis sonicated
  2. dissolutiondissolution
  3. filtrationThe reaction mixture is filtered over Celite® 545
  4. washthe filter residue is washed with additional MeOH
  5. customThe combined filtrates are partially evaporated under reduced pressure
  6. customa rotary evaporator
  7. customPurification by silica gel column chromatography with mixtures of (MeOH) and dichloromethane (DCM)

Sources & evidence

ORD record
ord-b770768c54f940c7b428b857717a86ea
Source dataset
uspto-grants-2016_07
Patent number
US09394236B2

Reaction notes

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