Sulfuric Acid → Acetylisatin

Participants

Reaction Conditions

Reaction Steps

A solution of 1-acetyl-5-amino-indoline (4.94 g, 28.03 mmol) in conc. HCl (250 mL) and H2O (17 mL) was added to a mixture of chloral hydrate (5.12 g, 31.0 mmol), and Na2SO4 (73.8 g, 0.52 mol) in H2O (68 mL). Once all materials were dissolved, hydroxylamine hydrochloride (6.27 g, 190 mmol) was added and the solution was heated to boiling over 30 minutes and maintained at a boil for 30 minutes. The precipitate which formed upon cooling to 20° C. was removed by filtration, washed with H2O, and dried in vacuo to constant mass to afford 6.68 g. of the 1-acetyl-5-[2-(isonitroso)acetamido]indoline (LC-MS: 248 (MH+)). This material was added in small portions over 30 minutes to conc. H2SO4 (20 mL) while stirring at 50° C. When the addition was complete the mixture was heated to 80° C. for 10 minutes, cooled to 20° C., and poured into ice/water (300 mL). The precipitate was filtered, washed with H2O and dried in vacuo to yield 6.02 g of the 1-acetyl isatin derivative (LC-MS: 248 (M+NH4+). A sample (2.68 g, 11.4 mmol) of this product was heated to 50° C. in dioxane (23 mL)/6N HCl (25 mL) for 16 hours. Concentration of the mixture in vacuo at 40° C. yielded the crude deacetyled isatin product (LC-MS: 189 (MH+)) which was redissolved in THF (50 mL) and reduced directly by addition of 1M borane/THF (114 mL, ~10 eq.). After stirring 16 hours at 20° C. the mixture was carefully quenched with H2O (50 mL), diluted with brine, and the pH adjusted to 10-11 before extraction with EtOAc. The organic extracts were pooled, dried over Na2 SO4(s), filtered and concentrated in vacuo. The residue was recrystallized from Et2O/hexanes to afford pure 1,2,3,5-tetrahydro-pyrrolo[2,3-f]indole (797 mg, LC-MS: 159 (MH+).

Provenance & Evidence