Tetrahydrofuran → Ethyl (4S)-2-ethyl-8-(methoxy)-6-[1-(methoxycarbonyl)vinyl]-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]-pyrazine-7-carboxylate

HRID 2114856Notes

Reaction equation

HRID 2114856 reaction equation
[CH2:1]([N:3]1[CH2:8][C@H:7]([CH3:9])[N:6]2[C:10]([C:20](=O)[C:21]([O:23][CH3:24])=[O:22])=[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:12]([O:13][CH3:14])=[C:5]2[C:4]1=[O:26])[CH3:2].[OH-].[Na+].[CH2:29]1COCC1>C1(C)C=CC=CC=1.CCOCC.[CH3-].C[Al+]C.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Ti+3]>[CH2:1]([N:3]1[CH2:8][C@H:7]([CH3:9])[N:6]2[C:10]([C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH2:29])=[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:12]([O:13][CH3:14])=[C:5]2[C:4]1=[O:26])[CH3:2]

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86612122Ethyl (4S)-2-ethyl-8-(methoxy)-6-[methoxy(oxo)acetyl]-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-7-carboxylate

Product 1

HCID 86612121Ethyl (4S)-2-ethyl-8-(methoxy)-6-[1-(methoxycarbonyl)vinyl]-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]-pyrazine-7-carboxylate

Reagents, catalysts & solvents 3

HCID 53384502mu-Chlorobis(eta5-cyclopentadienyl)(dimethylaluminum)-mu-methylenetitaniumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a cold (0° C.) solution of ethyl (4S)-2-ethyl-8-(methoxy)-6-[methoxy(oxo)-acetyl]-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]-pyrazine-7-carboxylate (1.0 g, 2.73 mmol) in anhydrous THF (100 mL), a solution of Tebbe reagent (6.0 mL, 0.5 M) in toluene was added. The reaction mixture was stirred at room temperature for one hour. The product mixture was diluted with ether (100 mL) and treated with aq sodium hydroxide (4 mL, 1M). The mixture was filtered. The organic extract was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with ethyl acetate-hexane gradient. Collection and concentration of appropriate fractions provided the olefination product.

Workup

  1. filtrationThe mixture was filtered
  2. extractionThe organic extract
  3. customwas separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. washeluted with ethyl acetate-hexane gradient
  8. customCollection and concentration of appropriate fractions
  9. customprovided the olefination product

Sources & evidence

ORD record
ord-88bcfb105a504d55a11bdd8834c21777
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

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