2-Methylindolizine → (5E)-4-methylidene-5-{(2E)-2-[(2-methylindolizin-3-yl)carbonyl]but-2-en-1-ylidene}-2-phenyl-4,5-dihydro-6H-1,3-oxazin-6-one

HRID 1502207Notes

Reaction equation

HRID 1502207 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[N:9]([CH:10]=1)[CH:8]=[CH:7][CH:6]=[CH:5]2.[CH2:11]=[C:12]1[N:13]=[C:14]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:15][C:16](=[O:25])/[C:17]/1=[CH:18]/[C:19](=[CH:23]\[CH3:24])/[C:20](Cl)=[O:21]>C1COCC1.C(OCC)(=O)C>[CH2:11]=[C:12]1[N:13]=[C:14]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:15][C:16](=[O:25])/[C:17]/1=[CH:18]/[C:19](/[C:20]([C:10]1[N:9]2[C:4]([CH:5]=[CH:6][CH:7]=[CH:8]2)=[CH:3][C:2]=1[CH3:1])=[O:21])=[CH:23]\[CH3:24]

Participants

5

Reactant 2

HCID 5826302-MethylindolizineHCID 117776641(2E)-2-[(E)-(4-methylidene-6-oxo-2-phenyl-4H-1,3-oxazin-5(6H)-ylidene)methyl]but-2-enoyl chloride

Product 1

HCID 89655795(5E)-4-methylidene-5-{(2E)-2-[(2-methylindolizin-3-yl)carbonyl]but-2-en-1-ylidene}-2-phenyl-4,5-dihydro-6H-1,3-oxazin-6-oneYield 69%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-methylindolizine (11.5 g; 87.7 mmol) in 35 mL of THF is added dropwise to a suspension of (2E)-2-[(E)-(4-methylidene-6-oxo-2-phenyl-4H-1,3-oxazin-5(6H)-ylidene)methyl]but-2-enoyl chloride (25 g; 87.7 mmol) in 140 mL of THF at 0° C. under nitrogen. After 18 h of stirring at ambient temperature, the reaction medium is diluted in ethyl acetate, and the solution is washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over sodium sulphate and concentrated to dryness. The residue obtained is purified by flash chromatography on silica (DCM) to give 22.75 g (69%) of a yellow powder.

Workup

  1. washthe solution is washed with a saturated aqueous solution of sodium hydrogen carbonate
  2. dry with materialdried over sodium sulphate
  3. concentrationconcentrated to dryness
  4. customThe residue obtained
  5. customis purified by flash chromatography on silica (DCM)

Sources & evidence

ORD record
ord-b98f1d3088e24120a923de8bddbca45f
Source dataset
uspto-grants-2015_12
Patent number
US09206177B2

Reaction notes

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