Phosphate → 1-Benzyl-3-bromomethyl-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid ethyl ester

HRID 919713Notes

Reaction equation

HRID 919713 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8](=[O:19])[C:7]=1[C:20](O)=O)=[O:5])[CH3:2].C(Cl)(=O)C(Cl)=O.[BH3-]C#N.[Na+].P([O-])([O-])([O-])=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:58]>C(Cl)Cl.CN(C=O)C.C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8](=[O:19])[C:7]=1[CH2:20][Br:58])=[O:5])[CH3:2]

Participants

10

Reactant 6

HCID 1061PhosphateHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 65578Oxalyl chlorideHCID 5003444Sodium cyanoborohydrideHCID 682975154-(Ethoxycarbonyl)-1-benzyl-1,2-dihydro-2-oxopyridine-3-carboxylic acid

Product 1

HCID 682971831-Benzyl-3-bromomethyl-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid ethyl esterYield 39.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

1-Benzyl-2-oxo-1,2-dihydro-pyridine-3,4-dicarboxylic acid 4-ethyl ester (581 mg, 1.93 mmol) was dissolved in 15 mL of CH2Cl2. Oxalyl chloride (1.7 mL, 19.3 mmol) and DMF (2 drops) were added, and the mixture was stirred for 2.5 h. Solvent and excess oxalyl chloride were removed by evaporation in vacuo, and to the residue was added a solution of NaCNBH3 (250 mg, 3.86 mmol) in THF (15 mL). The resulting suspension was stirred at r.t. for 16 h. The reaction mixture was cooled in an ice bath, and then poured into a pre-cooled, vigorously stirring pH 4.9 phosphate buffer (100 mL). The resulting mixture was extracted several times with benzene, and the combined organic layer was washed with ice-cold water and dried over MgSO4. Evaporation of the solvent at reduced pressure gave a viscous oil, which was dissolved in 10 mL of CH2Cl2. The solution was cooled in at ice bath, and triphenylphosphine (759 mg, 2.90 mmol) and carbon tetrabromide (960 mg, 2.90 mmol) were added. The mixture was then stirred at r.t. for 16 h. Solvent was evaporated in vacuo, and the residue was purified by silica gel chromatography (0-40% EtOAc/hexanes) to give 270 mg of the title compound as a yellow oil. 1H NMR (CDCl3, 200 MHz): δ=7.15-7.42 (m, 6H), 6.51 (d, 1H, J=7.2 Hz), 5.18 (s, 2H), 4.90 (s, 2H), 4.41 (q, 2H, J=7.0 Hz), 1.43 (t, 3H, J=7.0 Hz).

Workup

  1. customSolvent and excess oxalyl chloride were removed by evaporation in vacuo
  2. stirringThe resulting suspension was stirred at r.t. for 16 h
  3. temperatureThe reaction mixture was cooled in an ice bath
  4. additionpoured into a pre-cooled
  5. extractionThe resulting mixture was extracted several times with benzene
  6. washthe combined organic layer was washed with ice-cold water
  7. dry with materialdried over MgSO4
  8. customEvaporation of the solvent at reduced pressure
  9. customgave a viscous oil, which
  10. temperatureThe solution was cooled in at ice bath
  11. stirringThe mixture was then stirred at r.t. for 16 h
  12. customSolvent was evaporated in vacuo
  13. customthe residue was purified by silica gel chromatography (0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7b43df1b16404a9c96c037392302db92
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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