Sodium hydride → tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4-methoxybutanoate

HRID 56769Notes

Reaction equation

HRID 56769 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]2[C:17]([O:18][CH3:19])=[CH:16][NH:15][C:14](=[O:20])[CH:13]=2)[CH:5]=1.[CH3:21][O:22][CH2:23][CH2:24][CH:25](OS(C(F)(F)F)(=O)=O)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]>O1CCCC1>[Cl:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]2[C:17]([O:18][CH3:19])=[CH:16][N:15]([CH:25]([CH2:24][CH2:23][O:22][CH3:21])[C:26]([O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[O:27])[C:14](=[O:20])[CH:13]=2)[CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1176049354-Chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrileHCID 118877890tert-Butyl 4-methoxy-2-{[(trifluoromethyl)sulphonyl]oxy}butanoate

Product 1

HCID 117622851tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4-methoxybutanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A little at a time, 405 mg (10.1 mmol) of sodium hydride (60% in mineral oil) were added to a suspension of 2.4 g (9.2 mmol) of 4-chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile in 70 ml of tetrahydrofuran, and the mixture was stirred at RT for another 1 h. 4.45 g (13.8 mmol) of tert-butyl 4-methoxy-2-{[(trifluoromethyl)sulphonyl]oxy}butanoate (racemate) as a solution in 20 ml of THF were quickly added dropwise to the resulting reaction solution, and after the addition had ended the mixture was stirred at RT for another 1.5 h. The reaction was terminated by addition of 150 ml of saturated aqueous ammonium chloride solution and 150 ml of methyl tert-butyl ether. The phases were separated and the aqueous phase was extracted three times with 130 ml of methyl tert-butyl ether. The combined organic phases were dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (120 g silica cartridge, 85 ml/min, cyclohexane/ethyl acetate gradient), giving the title compound. Yield: 1.73 g (43% of theory)

Workup

  1. additionafter the addition
  2. stirringwas stirred at RT for another 1.5 h
  3. customThe reaction was terminated by addition of 150 ml of saturated aqueous ammonium chloride solution and 150 ml of methyl tert-butyl ether
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted three times with 130 ml of methyl tert-butyl ether
  6. dry with materialThe combined organic phases were dried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customThe crude product was purified by flash chromatography (120 g silica cartridge, 85 ml/min, cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-5381b7b96812401b9e0988344501b220
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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