Acetic Anhydride → 1-(5-Methoxyindolin-1-yl)ethanone

HRID 1014243Notes

Reaction equation

HRID 1014243 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH2:7][CH2:6]2.[C:12](OC(=O)C)(=[O:14])[CH3:13]>CN(C)C1C=CN=CC=1.ClCCl>[C:12]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[CH2:6][CH2:7]1)(=[O:14])[CH3:13]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 107019745-methoxy-2,3-dihydro-1H-indole

Product 1

HCID 126260911-(5-Methoxyindolin-1-yl)ethanoneYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A 4-neck 22L round bottom flask equipped with a reflux condenser, mechanical stirrer and thermowell was charged with 5-methoxyindoline (1520 g, ca. 10.2 mol) produced in accordance with Step A, immediately above and dichloromethane (15 L). To the solution was added 4-dimethylaminopyridine (50 g, 0.446 mol), followed by slow addition of acetic anhydride (1051 mL, 11.22 mol, 1.1 equiv, maintaining gentle reflux of the solvent). The reaction mixture was stirred at room temperature overnight. After completion, the reaction mixture was diluted with dichloromethane (10 L), then washed with water (15 L) and saturated sodium bicarbonate solution (15 L). The organic layer was dried over sodium sulfate and evaporated in vacuo to a crude solid, which was triturated from heptane (4 L) to afford 1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indole (1800 g, 92% yield over two steps). 1H-NMR (CDCl3, 300 MHz) δ 8.13 (d, J=6.3 Hz, 1H), 6.74-6.71 (m, 2 H), 4.05 (t, 2 H), 3.78 (s, 3 H), 3.17 (t, 2 H), 2.21 (s, 3 H).

Workup

  1. customproduced in accordance with Step A
  2. temperaturemaintaining gentle
  3. temperaturereflux of the solvent)
  4. washwashed with water (15 L) and saturated sodium bicarbonate solution (15 L)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customevaporated in vacuo to a crude solid, which
  7. customwas triturated from heptane (4 L)

Sources & evidence

ORD record
ord-561a66c381e74565846901d6ccf161ba
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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