HCID 59468910, compound → HCID 59468976, compound

HRID 1690102Notes

Reaction equation

HRID 1690102 reaction equation
[C:1]([CH2:3][C@@:4]1([C:30](OC)=[O:31])[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15]CC3C=CC=CC=3)[CH:10]=2)[N:5]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])#[N:2]>CO.[Ni]>[OH:15][C:11]1[CH:10]=[C:9]([C@H:6]2[CH2:7][CH2:8][C@:4]3([CH2:3][CH2:1][NH:2][C:30]3=[O:31])[N:5]2[C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 1

HCID 59468910HCID 59468910, compound

Product 1

HCID 59468976HCID 59468976, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-2-(cyanomethyl)-5-{3-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D44, 1.15 g, 2.55 mmol) in methanol (40 mL) was added Raney Nickel (slurry in water, 10 g) and the mixture was stirred under a hydrogen atmosphere (7 atm) for 4 hours. The catalyst was filtered off, the solvent removed under reduced pressure, and the solid residue was treated with toluene (3×20 mL) and dried under vacuum. The crude oil obtained was refluxed in methanol (100 mL) for 7 hours until a complete cyclization was observed. The solvent was removed under reduced pressure and the crude material purified by chromatography on silica gel using dichloromethane/methanol (100:0 to 95:5) to afford the title compound (0.41 g, 48%).

Workup

  1. filtrationThe catalyst was filtered off
  2. customthe solvent removed under reduced pressure
  3. additionthe solid residue was treated with toluene (3×20 mL)
  4. customdried under vacuum
  5. customThe crude oil obtained
  6. customThe solvent was removed under reduced pressure
  7. customthe crude material purified by chromatography on silica gel

Sources & evidence

ORD record
ord-196bb55aef2f474db214bd7d16a0b793
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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