Ethyl Acrylate → (4R,9aR)-6-(2-Ethoxycarbonyl-vinyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11919

Reaction equation

HRID 11919 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15](Br)=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[CH:24]=[CH2:25].C([O-])(=O)C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+]>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH:25]=[CH:24][C:23]([O:27][CH2:28][CH3:29])=[O:26])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester2×

Product 1

HCID 69557653(4R,9aR)-6-(2-Ethoxycarbonyl-vinyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 91.2%

Reagents, catalysts & solvents 2

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-CatalystHCID 1140TolueneSolvent

Procedure

To a solution of 1.0 g (2.71 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) and 0.36 ml (3.25 mmol) ethyl acrylate in 30 ml toluene were added 0.67 g (8.15 mmol) sodium acetate, 82.6 mg (0.27 mmol) tri(o-tolyl)phosphine and 0.04 mg (0.1 mmol) allylpalladium chloride dimer. The reaction mixture was heated under reflux for 20 h, then poured into saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with 10% aqueous citric acid solution and brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by column chromatography on silica gel (0.032–0.063 mm) with n-hexane:ethyl acetate (9:1) as eluant to afford the desired compound as a yellow solid (91.2%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 20 h
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with 10% aqueous citric acid solution and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by column chromatography on silica gel (0.032–0.063 mm) with n-hexane:ethyl acetate (9:1) as eluant

Sources & evidence

ORD record
ord-c7a4f3c997774bd4bc1869e396fb93b7
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Linked notes

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