Dimethylformamide → (4R,9aR)-7-formyl-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 1272130Notes

Reaction equation

HRID 1272130 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]([CH3:22])=[C:14](Br)[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(C)(C)C.CN(C)[CH:31]=[O:32].[Cl-].[NH4+]>C(OCC)C>[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]([CH3:22])=[C:14]([CH:31]=[O:32])[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 69357585(4R,9aR)-7-Bromo-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 86596359(4R,9aR)-7-formyl-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 80.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 0.41 g (1.07 mmol) (4R,9aR)-7-bromo-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (example 6, intermediate) in 28 mL diethyl ether was cooled to −100° C. and treated with 0.80 mL (1.18 mmol) tert-butyl lithium (1.5M solution in n-pentane). After 15 min. 0.12 mL N,N-dimethylformamide was added and the temperature was raised to −78° C. After 45 min. the solution was poured into 10% aqueous ammonium chloride solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and filtered. The solvent was removed at a rotary evaporator and the residue was purified by column chromatography on silica gel (0.040–0.063 mm) with ethyl acetate:n-hexane (1:2) as eluant to give the compound as a yellow foam (80.2%).

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. customThe solvent was removed at a rotary evaporator
  6. customthe residue was purified by column chromatography on silica gel (0.040–0.063 mm) with ethyl acetate:n-hexane (1:2) as eluant

Sources & evidence

ORD record
ord-10196703566141b0af667029ff22df4b
Source dataset
uspto-grants-2007_04
Patent number
US07208494B2

Reaction notes

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