Water → (R)-3-(6-Cyano-3-nitro-pyridin-2-ylamino)-3-phenyl-propionic acid ethyl ester

HRID 2175193Notes

Reaction equation

HRID 2175193 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C@@H:6]([NH:13][C:14]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[C:16](Cl)[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].O.CCOC(C)=O.[CH3:32][N:33](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C@@H:6]([NH:13][C:14]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[C:16]([C:32]#[N:33])[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 58497459(R)-3-(6-Chloro-3-nitro-pyridin-2-ylamino)-3-phenyl-propionic acid ethyl ester

Product 1

HCID 58497401(R)-3-(6-Cyano-3-nitro-pyridin-2-ylamino)-3-phenyl-propionic acid ethyl esterYield 96%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

In a microwave reaction vessel was dissolved (R)-3-(6-chloro-3-nitro-pyridin-2-ylamino)-3-phenyl-propionic acid ethyl ester (0.75 g, 2.14 mmol) in DMF (12 ml). Added the zinc cyanide (0.15 g, 1.29 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.25 g, 0.21 mmol). Reaction mixture was degassed using a stream of nitrogen and capped. Reaction was heated in a microwave at 120° C. for 1 hour and then stirred at room temperature for 72 hours. After this time the reaction was poured into water and EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3×). The combined organics were dried (MgSO4), filtered and concentrated to give the crude product which was purified via silica gel flash column chromatography (12 g silica gel, 5-20% EtOAc/hexanes) to afford 0.70 g (96%) of the title compound.

Workup

  1. customIn a microwave reaction vessel
  2. customReaction mixture
  3. customwas degassed
  4. customcapped
  5. customReaction
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with EtOAc (3×)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product which
  12. customwas purified via silica gel flash column chromatography (12 g silica gel, 5-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-57ff62f288d54a7185bfce06271e99f0
Source dataset
uspto-grants-2015_06
Patent number
US09062056B2

Reaction notes

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