Sodium hydride → Benzyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4,4-dimethylpentanoate

HRID 56807Notes

Reaction equation

HRID 56807 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][C:22]([CH3:44])([CH3:43])[CH2:23][CH:24](OS(C(F)(F)F)(=O)=O)[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C1COCC1>[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:24]([CH2:23][C:22]([CH3:44])([CH3:43])[CH3:21])[C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[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 117605463Benzyl 4,4-dimethyl-2-{[(trifluoromethyl)sulphonyl]oxy}pentanoate

Product 1

HCID 118877930Benzyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4,4-dimethylpentanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A little at a time, 41.8 mg (1.04 mmol) of sodium hydride (60% in mineral oil) were added to a suspension of 261 mg (purity 87%, 870 μmol) of 4-chloro-2-(5-methoxy-2-oxo-1,2-dihydropyridin-4-yl)benzonitrile in 10 ml of THF, and the mixture was stirred at RT for another 1 h. 481 mg (1.31 mmol) of benzyl 4,4-dimethyl-2-{[(trifluoromethyl)sulphonyl]oxy}pentanoate (racemate) as a solution in 3 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 10 ml of saturated aqueous ammonium chloride solution and 15 ml of methyl tert-butyl ether. The phases were separated and the aqueous phase was extracted three times with 10 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 (80 g silica cartridge, 60 ml/min, cyclohexane/ethyl acetate gradient). Yield: 294 mg (71% 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 10 ml of saturated aqueous ammonium chloride solution and 15 ml of methyl tert-butyl ether
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted three times with 10 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 (80 g silica cartridge, 60 ml/min, cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-0551a7689a8048c49d9ceb22ae79d5c9
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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