HCID 58911261, compound → HCID 86598936, compound

HRID 2358231Notes

Reaction equation

HRID 2358231 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[CH2:5][CH:6]([C:11]1[C:16](Br)=[CH:15][C:14]([F:18])=[C:13]([N:19]=[N:20][N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:12]=1[F:26])[CH2:7][N+:8]([O-])=O)[CH3:2]>CCN(CC)CC.C(O)C.[Ni]>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][CH:6]([C:11]1[CH:16]=[CH:15][C:14]([F:18])=[C:13]([N:19]=[N:20][N:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)[C:12]=1[F:26])[CH2:7][NH2:8])[CH3:2]

Participants

5

Reactant 1

HCID 58911261HCID 58911261, compound

Product 1

HCID 86598936HCID 86598936, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 702EthanolSolventHCID 8471TriethylamineSolvent

Procedure

In a 500 ml pressure jar, under inert atmosphere, 6.29 g (14 mmol) of 3-[6-bromo-2,4-difluoro-3-(pyrrolidin-1-ylazo)-phenyl]-4-nitro-butyric acid ethyl ester all and Et3N (5.9 ml) are dissolved in 120 ml of ethanol. A suspension of 6 g of predried (3 times, ethanol) Raney nickel is added and the mixture hydrogenated on a Parr hydrogenator at a maximum of 20 psi H2 pressure (strongly exothermically reaction, ice/water cooling required). The mixture is degassed, filtered on a Celite/Norite pad, and the filtrate concentrated in vacuo, to give 6.2 g of crude. It is again hydrogenated as described above to remove the bromide using 0.59 g of Pd/C instead of Raney nickel during 0.75 h on a Parr hydrogenator at a maximum of 40 psi H2 pressure. The crude amino-ester is purified by chromatography on silicagel (CH2Cl2/EtOH/NH4OH: 94.5/5/0.5 (v/v/v)) to give 3.6 g of 4-amino-3-[2,4-difluoro-3-(pyrrolidin-1-ylazo)-phenyl]-butyric acid ethyl ester a12 (76% yield) used as such in the next step.

Workup

  1. additionis added
  2. customThe mixture is degassed
  3. filtrationfiltered on a Celite/Norite pad
  4. concentrationthe filtrate concentrated in vacuo
  5. customto give 6.2 g of crude
  6. customto remove the bromide using 0.59 g of Pd/C instead of Raney nickel during 0.75 h on a Parr hydrogenator at a maximum of 40 psi H2 pressure
  7. customThe crude amino-ester is purified by chromatography on silicagel (CH2Cl2/EtOH/NH4OH: 94.5/5/0.5 (v/v/v))

Sources & evidence

ORD record
ord-82a99f2ff5c74af19e8c26c34fb5760c
Source dataset
uspto-grants-2010_07
Patent number
US07763644B2

Reaction notes

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