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 1272138Notes

Reaction equation

HRID 1272138 reaction equation
CCO[C:4]([C:6]1[N:23]([C:24](OC(C)(C)C)=O)[C:9]2=[N:10][CH:11]=[C:12](OC(=O)C3C=CC=CC=3)[CH:13]=[C:8]2[CH:7]=1)=O.[C:31]([Li])(C)(C)C.[CH3:36][N:37](C)[CH:38]=[O:39].C(O)(=O)[CH2:42][C:43]([CH2:48]C(O)=O)([C:45](O)=O)[OH:44].[O:54]1CCC[CH2:55]1>>[C:43]([O:44][C:38]([N:37]1[CH2:36][C@@H:24]([CH3:31])[N:23]2[C@H:6]([CH2:7][C:8]3[C:9]2=[N:10][C:11]([CH:55]=[O:54])=[CH:12][CH:13]=3)[CH2:4]1)=[O:39])([CH3:42])([CH3:45])[CH3:48]

Participants

6

Reactant 5

HCID 311Citric AcidHCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 693563741H-Pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid, 5-(benzoyloxy)-, 1-(1,1-dimethylethyl) 2-ethyl 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%

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 c) 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 on 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 remaining residue was purified by flash column chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant to give 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 remaining residue was purified by flash column chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant

Sources & evidence

ORD record
ord-ce86f1dc4dd94653b2998c60ae82b374
Source dataset
uspto-grants-2007_04
Patent number
US07208494B2

Reaction notes

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