HCID 59468979, compound → HCID 59468978, compound

HRID 1690119Notes

Reaction equation

HRID 1690119 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 59468979HCID 59468979, compound

Product 1

HCID 59468978HCID 59468978, compoundYield 35.2%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5S)-2-(cyanomethyl)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D77, 500 mg, 1.11 mmol) in methanol (30 ml) was added Raney Nickel (slurry in water, 1 spatula) and the mixture was stirred under a hydrogen atmosphere (6 atm) for 6 hours. The catalyst was filtered off, the solvent removed under reduced pressure, and the solid residue was treated two times with toluene and dried under vacuum. The dry white solid obtained was refluxed in methanol (30 ml) for six 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 (1:0 to 92:8) to afford the title compound as a white solid (130 mg, 35%); Rt (HPLC): 3.89 min; Rf (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 two times with toluene
  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-c14f74d7721a4782a2da59732d58fb12
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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