Sodium hydride → tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-ethyloxetan-3-yl)prop-2-enoate

HRID 56873Notes

Reaction equation

HRID 56873 reaction equation
[H-].[Na+].[CH2:3]([C:5]1([CH:9]=O)[CH2:8][O:7][CH2:6]1)[CH3:4].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:35]#[N:36])=[C:16]([C:18]2[C:23]([O:24][CH3:25])=[CH:22][N:21]([CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:20](=[O:34])[CH:19]=2)[CH:17]=1>CN(C)C=O>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:35]#[N:36])=[C:16]([C:18]2[C:23]([O:24][CH3:25])=[CH:22][N:21]([C:26](=[CH:9][C:5]3([CH2:3][CH3:4])[CH2:6][O:7][CH2:8]3)[C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[C:20](=[O:34])[CH:19]=2)[CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 534845673-Ethyloxetane-3-carbaldehydeHCID 117622654tert-Butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate

Product 1

HCID 118877902tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-ethyloxetan-3-yl)prop-2-enoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

38.4 mg (1.60 mmol, 2 eq., 60% in mineral oil) of sodium hydride and 457 mg (4.00 mmol) of 3-ethyloxetane-3-carbaldehyde in 1 ml of dimethylformamide were added in succession to a solution of 300 mg (800 μmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate in 8 ml of dimethylformamide. After 15 min at RT, the reaction was terminated by addition of 10 ml of saturated aqueous ammonium chloride solution and the reaction mixture was then extracted three times with 20 ml of ethyl acetate. The combined organic phases were dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography (24 g cartridge, 35 ml/min, cyclohexane/ethyl acetate gradient). Yield: 320 mg (82% of theory)

Workup

  1. customthe reaction was terminated by addition of 10 ml of saturated aqueous ammonium chloride solution
  2. extractionthe reaction mixture was then extracted three times with 20 ml of ethyl acetate
  3. dry with materialThe combined organic phases were dried over magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by flash chromatography (24 g cartridge, 35 ml/min, cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-9b294dfd4fb045e29bec3b844a312269
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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