(3-Cyanopyridin-2-ylamino)-acetic acid ethyl ester → (3-Formylpyridin-2-ylamino)acetic acid ethyl ester

HRID 1362357Notes

Reaction equation

HRID 1362357 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][NH:6][C:7]1[C:12]([C:13]#N)=[CH:11][CH:10]=[CH:9][N:8]=1)[CH3:2].[PH2]([O-])=[O:17].[Na+]>[Ni].O.CC(O)=O.N1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:15])[CH2:5][NH:6][C:7]1[C:12]([CH:13]=[O:17])=[CH:11][CH:10]=[CH:9][N:8]=1)[CH3:2]

Participants

5

Reactant 2

HCID 14456218(3-Cyanopyridin-2-ylamino)-acetic acid ethyl esterHCID 178527019HCID 178527019, compound

Product 1

HCID 59277533(3-Formylpyridin-2-ylamino)acetic acid ethyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 67720230HCID 67720230, compoundSolvent

Procedure

(3-Cyanopyridin-2-ylamino)acetic acid ethyl ester (2.6 g, 12.6 mmol) was dissolved into a 1:1:2 mixture of H2O/CH3COOH/pyridine (75 mL) under argon. Sodium hypophosphite (5.0 g) and Raney nickel (2.0 g) were added and the mixture was stirred at room temperature for 3 h. The slurry was filtered through a bed of celite and the filter cake was washed with water. Concentrated NH4OH was added to the filtrate until pH 10 was reached. The solution was extracted with ethyl acetate (4×50 mL). The organic phase was washed with brine (50 mL), dried over MgSO4 and concentrated. The product was purified by silica gel chromatography (CH2Cl2/EtOAc 9:1) to give the title compound as a clear yellow oil (2.16 g, 83%). 1H NMR (300 MHz, CDCl3) δ 9.86 (s, 1H), 8.69 (bs, 1H), 8.31 (dd, J=4.8, 1.9 Hz, 1H), 7.79 (dd, J=7.6, 2.0 Hz, 1H), 6.72 (dd, J=7.6, 4.8 Hz, 1H), 4.32 (d, J=5.5 Hz, 2H), 4.24 (q, J=7.0 Hz, 2H), 1.29 (t, J=7.2 Hz, 3H).

Workup

  1. filtrationThe slurry was filtered through a bed of celite
  2. washthe filter cake was washed with water
  3. additionConcentrated NH4OH was added to the filtrate until pH 10
  4. extractionThe solution was extracted with ethyl acetate (4×50 mL)
  5. washThe organic phase was washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe product was purified by silica gel chromatography (CH2Cl2/EtOAc 9:1)

Sources & evidence

ORD record
ord-72edacaf30fe4caf914c2e909d1d3fd7
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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