HCID 59468929, compound → HCID 59468973, compound

HRID 1690092Notes

Reaction equation

HRID 1690092 reaction equation
[C:1]([CH2:3][C@@:4]1([C:30]([O:32]C)=O)[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15]CC3C=CC=CC=3)=[CH:11][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:12]1[CH:13]=[CH:14][C:9]([C@H:6]2[CH2:7][CH2:8][C@:4]3([CH2:3][CH2:1][NH:2][C:30]3=[O:32])[N:5]2[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])=[CH:10][CH:11]=1

Participants

4

Reactant 1

HCID 59468929HCID 59468929, compound

Product 1

HCID 59468973HCID 59468973, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-2-(cyanomethyl)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D24, 2.7 g, 5.99 mmol): in methanol (50 ml) was added Raney Nickel (slurry in water) and the mixture was stirred under a hydrogen atmosphere (7 atmospheres) for 14 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 dry white solid obtained was refluxed in methanol (40 ml) for five hours until cyclization was complete. The solvent was removed under reduced pressure and the crude material purified by chromatography on silica gel using dichloromethane/methanol (95:5 to 90:10) to afford the title compound as a white solid (1.35 g, 68%); Rt (HPLC): 3.91 min; R (dichloromethane:methanol=9:1): 0.41; MS: (ES/+) m/z: 665 [2M+Na+], 355 [M+Na+]; C18H24N2O4 requires 332; 1H NMR (400 MHz, DMSO-d6) δ(ppm): 9.11 (s, 1H); 7.76 and 7.66 (s, s, 1H); 7.43 (dd, 2H); 6.66 (dd, 2H); 4.81-4.70 (m, 1H); 3.29-3.20 (m, 1H); 3.19-3.09 (m, 1H); 2.47-2.20 (m, 2H); 2.08-1.85 (m, 2H); 1.84-1.74 (m, 1H); 1.68-1.52 (m, 1H); 1.33 and 1.08 (s, s, 9H).

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 dry white solid obtained
  6. customThe solvent was removed under reduced pressure
  7. customthe crude material purified by chromatography on silica gel

Sources & evidence

ORD record
ord-30672259b21d461aa434dd286f3e50c9
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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