Sodium hydride → Ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate

HRID 1503722Notes

Reaction equation

HRID 1503722 reaction equation
C1(C(=[N:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])C2C=CC=CC=2)C=CC=CC=1.[H-].[Na+].[Br:23][C:24]1[CH:25]=[C:26]([Cl:31])[C:27](Cl)=[N:28][CH:29]=1>CN(C=O)C>[NH2:14][CH:15]([C:27]1[C:26]([Cl:31])=[CH:25][C:24]([Br:23])=[CH:29][N:28]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 127477605-Bromo-2,3-dichloropyridine

Product 1

HCID 71138503Ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetateYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl 2-(diphenylmethyleneamino)acetate (10.2 g, 38.2 mmol) was added to sodium hydride (NaH; 3.18 g, 133.52 mmol) in DMF (50 mL) at 0° C., and the mixture was stirred for 30 min. To this was added 5-bromo-2,3-dichloropyridine (12.9 g, 57.23 mmol), and the reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was quenched with 2 N HCl solution and then stirred for 4 h at ambient temperature. The mixture was extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as a liquid (1.3 g, 20%): 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.89 (s, 1H), 5.09 (s1H), 4.23 (m, 2H), 2.27 (br s, 2H), 1.26 (m, 3H); ESIMS m/z 293.05 ([M+H]+); IR (thin film) 3381, 3306, 1742, 759, 523 cm−1.

Workup

  1. stirringthe reaction mixture was stirred for 3 h at ambient temperature
  2. customThe reaction mixture was quenched with 2 N HCl solution
  3. stirringstirred for 4 h at ambient temperature
  4. extractionThe mixture was extracted with EtOAc
  5. washThe combined EtOAc layer was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (20-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-e0790a077c4a46c087183e5f2bf74351
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

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