Hydrochloric Acid → Ethyl 6-acetyl-8-(benzyloxy)-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

HRID 494085Notes

Reaction equation

HRID 494085 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:11](Br)[N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:14](=[O:26])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C1CCCCC1)C1CCCCC1.[CH:47]([O:49]CCCC)=[CH2:48].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Cl>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:47]([C:11]1[N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:14](=[O:26])[C:13]2=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:10]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29])(=[O:49])[CH3:48]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 24210N-Methyl dicyclohexylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 68864116Ethyl 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

Product 1

HCID 68865319Ethyl 6-acetyl-8-(benzyloxy)-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of ethyl 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate (0.32 g, 0.64 mmol) and N-methyldicyclohexylamine (0.20 mL, 0.96 mmol) in dioxane (1 mL) was purged with nitrogen for 5 minutes, n-butyl vinyl ether (0.83 mL, 6.4 mmol), tris(dibenzylidene-acetone)dipalladium (0.12 g, 0.13 mmol), and tri-tert-butylphosphine (0.065 g, 0.32 mmol) were added. After stirring at room temperature for 2 days, the reaction mixture was treated with 1 N HCl and stirred at room temperature overnight. The reaction mixture was partitioned between chloroform and brine. The organic extract was dried over sodium sulfate, filtered and concentrated. The residue was subjected to column chromatography on silica gel eluted with a hexanes and ethyl acetate gradient to provide titled product.

Workup

  1. stirringstirred at room temperature overnight
  2. customThe reaction mixture was partitioned between chloroform and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washeluted with a hexanes and ethyl acetate gradient

Sources & evidence

ORD record
ord-1dfb6bfd4043417da6b589cd41374b83
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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