Dimethylformamide → t-Butyl 5-nitroindole-2-carboxylate

HRID 2054712Notes

Reaction equation

HRID 2054712 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([OH:15])=[O:14])=[CH:7]2)([O-:3])=[O:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[CH3:27][C:28]([CH3:31])([O-])[CH3:29].[K+]>C1COCC1>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([O:15][C:28]([CH3:31])([CH3:29])[CH3:27])=[O:14])=[CH:7]2)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 3512915-Nitroindole-2-carboxylic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 10801431t-Butyl 5-nitroindole-2-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

To a stirred solution of 9 (12.8 g, 61.2 mmol) in dry THF (200 mL) under argon was added oxalyl chloride (12.0 mL, 137.5 mmol) followed by DMF (0.1 mL), which caused a vigorous evolution of gas. After 40 min, the reaction mixture was evaporated to dryness. The resulting solid was re-dissolved in THF (150 mL), cooled to ˜30° C., and stirred under argon. A solution of potassium t-butoxide (1.0 M in THF, 140 mL, 140 mmol) was then added dropwise over 45 min, and stirring was continued for an additional 45 min. The reaction was quenched with 600 mL of water, neutralized with few drops of a 10% aqueous solution of H3PO4 and extracted with ethyl acetate (3×400 mL). The organic extracts were washed with saturated aqueous NaHCO3, water, and then dried over magnesium sulfate, filtered, concentrated and crystallized with ethanol/hexane to afford compound 10 (9.62 g, 85% yield). Rf=0.35 (1:5 Ethyl acetate/Hexane); 1H NMR (CDCl3), 11.63 (s, 1H), 8.66 (dd, 1H, J=0.5, 1.3 Hz), 8.20 (dd, 1H, J=0.5, 9.0 Hz), 7.48 (dd, 1H, J=0.5, 9.1 Hz), 7.28 (dd, 1H, J=0.9, 11.1 Hz), 1.63 (s, 9H); 13C NMR 160.39, 142.12, 138.11, 132.10, 126.78, 120.22, 119.83, 111.98, 109.82, 82.91, 28.26; MS m/z 285.43 (M+Na)+.

Workup

  1. customthe reaction mixture was evaporated to dryness
  2. dissolutionThe resulting solid was re-dissolved in THF (150 mL)
  3. stirringstirring
  4. waitwas continued for an additional 45 min
  5. customThe reaction was quenched with 600 mL of water
  6. extractionextracted with ethyl acetate (3×400 mL)
  7. washThe organic extracts were washed with saturated aqueous NaHCO3, water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customcrystallized with ethanol/hexane

Sources & evidence

ORD record
ord-c661bf2d166e4218b9ddcfc3291f6a08
Source dataset
uspto-grants-2008_02
Patent number
US07329760B2

Reaction notes

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