ethyl 5-bromo-8-carbamoyl-9H-carbazole-2-carboxylate → 4-bromo-7-(1-hydroxycyclopropyl)-9H-carbazole-1-carboxamide

HRID 1811147Notes

Reaction equation

HRID 1811147 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[NH2:16])=[C:11]2[C:3]=1[C:4]1[CH:5]=[CH:6][C:7]([C:18]([O:20]CC)=O)=[CH:8][C:9]=1[NH:10]2.[CH2:23]([Mg]Cl)[CH3:24]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O>[Br:1][C:2]1[C:3]2[C:4]3[C:9](=[CH:8][C:7]([C:18]4([OH:20])[CH2:24][CH2:23]4)=[CH:6][CH:5]=3)[NH:10][C:11]=2[C:12]([C:15]([NH2:16])=[O:17])=[CH:13][CH:14]=1

Participants

5

Reactant 2

HCID 59375100ethyl 5-bromo-8-carbamoyl-9H-carbazole-2-carboxylate2×HCID 178461633HCID 178461633, compound

Product 1

HCID 666060564-bromo-7-(1-hydroxycyclopropyl)-9H-carbazole-1-carboxamideYield 83.7%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 962WaterSolvent

Procedure

Step 1 A solution of ethyl 5-bromo-8-carbamoyl-9H-carbazole-2-carboxylate (Intermediate 48-1, 0.275 g, 0.761 mmol) was treated with titanium (IV) isopropoxide (0.31 mL, 1.07 mmol), followed by ethylmagnesium chloride (2 M in THF, 3.81 mL, 7.61 mmol). The mixture was stirred at rt for 1 h, then was cooled on ice and treated with water (10 mL). After 30 min, the solid was removed by filtration and rinsed with ether (150 mL). The organic layer was dried and concentrated to give 4-bromo-7-(1-hydroxycyclopropyl)-9H-carbazole-1-carboxamide as a yellow solid (0.220 g, 79%). 1H NMR (400 MHz, DMSO-d6) δ 11.65 (1 H, s), 8.52 (1 H, d, J=8.4 Hz), 8.25 (1 H, br. s.), 7.84-7.89 (2 H, m), 7.61 (1 H, br. s.), 7.45 (1 H, d, J=8.1 Hz), 7.13 (1 H, dd, J=8.5, 1.7 Hz), 6.11 (1 H, s), 1.21-1.27 (2 H, m), 1.06-1.11 (2 H, m).

Workup

  1. temperaturewas cooled on ice
  2. waitAfter 30 min
  3. customthe solid was removed by filtration
  4. washrinsed with ether (150 mL)
  5. customThe organic layer was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6e7b586d379c4deb8ebf493098d00313
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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