Hydrochloric Acid → 5-methoxy-6-nitro-2,3-dihydro-1H-indole
Reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:16][CH3:17])=[C:10]([N+:13]([O-:15])=[O:14])[CH:11]=2)[CH2:6][CH2:5]1)(=O)C.Cl.[OH-].[Na+]>>[CH3:17][O:16][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][C:10]=1[N+:13]([O-:15])=[O:14])[NH:4][CH2:5][CH2:6]2Participants
Procedure
A roundbottom flask equipped with a reflux condenser, mechanical stirrer and thermowell was charged with 1-acetyl-5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole (954 g, 4.04 mol) produced in accordance with Step C, immediately above, and aqueous 6N hydrochloric acid (9.5 L). The resulting suspension was heated to reflux for 4 hrs (became clear solution after 2 hrs). The reaction mixture was allowed to cool to room temperature then sodium hydroxide (50% w/w) was added to adjust the pH to 10. The resulting mixture was extracted with ethyl acetate (3×10L). The combined organic layers were washed with saturated potassium carbonate solution (10 L) and brine (10 L), then dried over sodium sulfate, evaporated in vacuo to afford 5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole (737 g, 94%), which was used for the next step without further purification. 1H-NMR (DMSO, 300 MHz) δ 7.11 (s, 1H), 6.87 (s, 1H), 5.59 (brs, 1H), 3.78 (s, 3H), 3.43 (t, 2H), 2.97 (t, 2H).
Workup
- customA roundbottom flask equipped with a reflux condenser, mechanical stirrer
- customproduced in accordance with Step C
- temperatureThe resulting suspension was heated
- temperatureto reflux for 4 hrs (became clear solution after 2 hrs)
- extractionThe resulting mixture was extracted with ethyl acetate (3×10L)
- washThe combined organic layers were washed with saturated potassium carbonate solution (10 L) and brine (10 L)
- dry with materialdried over sodium sulfate
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-a00671cb43194c49b7d4b935155b0764
- Source dataset
- uspto-grants-2011_07
- Patent number
- US07981903B2
Reaction notes
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