1-Methylcyclopropane-1-carbaldehyde → tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(1-methylcyclopropyl)prop-2-enoate

HRID 56814Notes

Reaction equation

HRID 56814 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1.[CH3:27][C:28]1([CH:31]=O)[CH2:30][CH2:29]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([C:16](=[CH:27][C:28]3([CH3:31])[CH2:30][CH2:29]3)[C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 101976191-Methylcyclopropane-1-carbaldehydeHCID 117622654tert-Butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate

Product 1

HCID 118877868tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(1-methylcyclopropyl)prop-2-enoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

At −78° C., 1.87 ml (1.87 mmol) of bis(trimethylsilyl)lithium amide (1M in THF) were added dropwise to a solution of 500 mg (1.33 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate in 10 ml of THF, and the mixture was stirred for another 10 min 488 mg (5.80 mmol) of 1-methylcyclopropanecarbaldehyde were then added, and after a further 10 min the mixture was warmed to −20° C. After 3 h at −20° C., the reaction was terminated by addition of 30 ml of saturated aqueous ammonium chloride solution and the reaction mixture was extracted three times with 20 ml of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The residue was taken up in a little dichloromethane and purified by flash chromatography (24 g silica cartridge, 35 ml/min, cyclohexane/ethyl acetate gradient). Yield: 257 mg (44% of theory)

Workup

  1. additionwere then added
  2. customthe reaction was terminated by addition of 30 ml of saturated aqueous ammonium chloride solution
  3. extractionthe reaction mixture was extracted three times with 20 ml of ethyl acetate
  4. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. custompurified by flash chromatography (24 g silica cartridge, 35 ml/min, cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-7e279f17d45447e69d6607a544f3cbe3
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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