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

HRID 11944Notes

Reaction equation

HRID 11944 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]([CH2:22][OH:23])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(C)(C)C.CN(C)C=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[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:22]=[O:23])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6228DimethylformamideHCID 67238448(4R,9aR)-6-hydroxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester2×HCID 178418306HCID 178418306, compound

Product 1

HCID 86596361(4R,9aR)-6-Formyl-4-methyl-3,4,9,9a-tetrahydro-1 H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 40.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2.0 g (5.43 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 15 ml tetrahydrofuran was cooled to −75 deg C. and treated with 4.40 ml (0.65 mmol) tert-butyllithium (1.5 M solution in n-pentane). After 30 min, 0.60 ml (0.63 g, 8.15 mmol) N,N-dimethylformamide was added dropwise. After 2.5 h the reaction mixture was poured onto 10% aqueous citric acid solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash-chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant to afford the desired compound as a yellow oil (40.1%).

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by flash-chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant

Sources & evidence

ORD record
ord-a46fdafabe5249c698e36d7e815a119f
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Reaction notes

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