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

HRID 11922

Reaction equation

HRID 11922 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].[Cu][C:24]#[N:25]>O1CCOCC1.[C-]#N.C([N+](CC)(CC)CC)C.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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[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]([C:24]#[N:25])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 2

HCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester2×HCID 178418546HCID 178418546, compound

Product 1

HCID 69556656(4R,9aR)-6-Cyano-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 98.4%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 3014735Tetraethylammonium cyanideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 0.20 g (0.54 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) in 5 ml dioxane were added 195.0 mg (2.17 mmol) copper(I)cyanide, 22.5 mg (22 μmol) tris(dibenzylideneacetone)dipalladium(0), 48.2 mg (87 μmol) 1,1′-bis(diphenylphosphino)ferrocene and 0.13 g (0.81 mmol) tetraethylammonium cyanide and the suspension was heated to reflux and stirred for 1.5 h. The mixture was cooled to room temperature, filtered and the filtrate was washed successively with aqueous saturated sodium bicarbonate solution, aqueous 10% citric acid solution, brine, dried over magnesium sulfate, filtered and evaporated. The residue was immediately purified by flash column chromatography on silica gel (0.032–0.063 mm) to afford the desired compound as a colorless foam (98.4%).

Workup

  1. temperaturethe suspension was heated
  2. temperatureto reflux
  3. filtrationfiltered
  4. washthe filtrate was washed successively with aqueous saturated sodium bicarbonate solution, aqueous 10% citric acid solution, brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was immediately purified by flash column chromatography on silica gel (0.032–0.063 mm)

Sources & evidence

ORD record
ord-22ed86cfb9ec4e0589ebac4532874db4
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Linked notes

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