HCID 58169868, compound → HCID 58169920, compound

HRID 472693Notes

Reaction equation

HRID 472693 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:45])[C:16]([N:18]2[CH2:23][CH2:22][C@@:21]([CH:27]([CH2:32][C:33]([O:35]C)=O)[C:28]([O:30][CH3:31])=[O:29])([N+:24]([O-])=O)[CH2:20][C@@H:19]2[C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[CH3:44])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1>CO.[Ni]>[F:46][C:2]([F:47])([F:1])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:45])[C:16]([N:18]2[CH2:23][CH2:22][C@@:21]3([NH:24][C:33](=[O:35])[CH2:32][CH:27]3[C:28]([O:30][CH3:31])=[O:29])[CH2:20][C@@H:19]2[C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[CH3:44])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

4

Reactant 1

HCID 58169868HCID 58169868, compound2×

Product 1

HCID 58169920HCID 58169920, compoundYield 30.8%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

Dimethyl 2-[(2R,4R)-1-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-2-(4-fluoro-2-methylphenyl)-4-nitro-4-piperidinyl]butanedioate (Intermediate 39, 250 mg, 0.368 mmol) was dissolved in Methanol (6 ml) and to this solution was added Raney®-Nickel. The reaction mixture was left stirring under H2 at 1 atm for 3 hrs. The solid was filtered out and the solution was refluxed for 2 hrs. The solvent was removed in vacuo and the crude purified by Flash Chromatography (SP4, 25M cartridge, eluent from 90%:10% to 70%:30% Cy:EtOAc). The solvent was removed in vacuo obtaining the title compound (70 mg, 0.113 mmol, 30.8% yield) as a mixture of diastereoisomers. UPLC: Rt=0.83 mins, nm/z=618 [M+H]+.

Workup

  1. waitThe reaction mixture was left
  2. filtrationThe solid was filtered out
  3. temperaturethe solution was refluxed for 2 hrs
  4. customThe solvent was removed in vacuo
  5. customthe crude purified by Flash Chromatography (SP4, 25M cartridge, eluent from 90%:10% to 70%:30% Cy:EtOAc)
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a203a86fb1da4048a219b82556256dc4
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

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