2-(2-Cyano-3-methylamino-4-nitrophenyl)-2-methyl-3-oxobutyric acid ethyl ester → 2-(4-Amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester

HRID 1863894Notes

Reaction equation

HRID 1863894 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5]([C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[C:12]([NH:19][CH3:20])[C:11]=1[C:21]#[N:22])([CH3:9])[C:6](=[O:8])[CH3:7])[CH3:2]>CCOC(C)=O.[Pd]>[CH2:1]([O:3][C:4](=[O:23])[C:5]([C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([NH:19][CH3:20])[C:11]=1[C:21]#[N:22])([CH3:9])[C:6](=[O:8])[CH3:7])[CH3:2]

Participants

4

Reactant 1

HCID 120354712-(2-Cyano-3-methylamino-4-nitrophenyl)-2-methyl-3-oxobutyric acid ethyl ester

Product 1

HCID 110661612-(4-Amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl esterYield 107%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a 500 mL Parr pressure flask was added 2-(2-cyano-3-methylamino-4-nitro-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester (7.13 g, 16.5 mmol) as a solution in EtOAc (50 mL) followed by 10% palladium on carbon (1.0 g). The flask was purged under vacuum, then charged with hydrogen gas (50 psi). The flask was agitated at room temperature for while open to the ballast (caution: potential exotherm). After 8 hours, TLC analysis indicated that all starting material has been consumed. The reaction mixture was filtered through a pad of celite and washed with EtOAc. The resulting solution was concentrated to provide 2-(4-amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester (5.11 g, 77%) as a gray solid, which was used without further purification. 1H NMR (400 MHz, d6-DMSO) δ 6.70 (d, J=8.2 Hz, 1H), 6.33 (d, J=8.2 Hz, 1H), 6.17 (s, 2H), 4.90 (q, J1=5.1 Hz, J2=10.6 Hz, 1H), 4.21-4.15 (m, 2H), 2.95 (d, J=5.5 Hz, 2H), 2.22 (s, 3H), 1.66 (s, 3H), 1.2 (t, J=7.0 Hz, 3H).

Workup

  1. customThe flask was purged under vacuum
  2. additioncharged with hydrogen gas (50 psi)
  3. customhas been consumed
  4. filtrationThe reaction mixture was filtered through a pad of celite
  5. washwashed with EtOAc
  6. concentrationThe resulting solution was concentrated

Sources & evidence

ORD record
ord-0302b6103d884549932f417c77e9aa25
Source dataset
uspto-grants-2009_12
Patent number
US07625880B2

Reaction notes

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