Cesium carbonate → 2-tert-butyl-1-(2-hydroxyethyl)-5-nitro-1H-indole-4-carbonitrile
Reaction equation
[C:1]([C:5]1[NH:6][C:7]2[CH:8]=[CH:9][C:10]([N+:16]([O-:18])=[O:17])=[C:11]([C:14]#[N:15])[C:12]=2[CH:13]=1)([CH3:4])([CH3:3])[CH3:2].I[CH2:20][CH2:21][OH:22].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]([C:5]1[N:6]([CH2:20][CH2:21][OH:22])[C:7]2[CH:8]=[CH:9][C:10]([N+:16]([O-:18])=[O:17])=[C:11]([C:14]#[N:15])[C:12]=2[CH:13]=1)([CH3:4])([CH3:2])[CH3:3]Participants
Conditions
- Temperature
- 90 °C
Procedure
A mixture of 2-tert-butyl-5-nitro-1H-indole-4-carbonitrile (200 mg, 0.82 mmol), 2-iodoethanol (77 μL, 0.98 mmol), cesium carbonate (534 mg, 1.64 mmol) and DMF (1.3 mL) was heated to 90° C. overnight. Then more 2-iodoethanol (77 μL, 0.98 mmol) was added and the reaction was stirred at 90° C. for 3 days. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was washed with ethyl acetate and then the combined ethyl acetate layers were washed with water (×3) and brine, dried over MgSO4 and concentrated. The residue was purified by column chromatography (50-100% CH2Cl2-Hexanes) to yield the product as a yellow solid (180 mg, ˜25% purity by NMR, product co-elutes with the indole starting material). ESI-MS m/z calc. 287.1, found 288.5 (M+1)+. Retention time 1.59 minutes. 1H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 8.14 (d, J=9.1 Hz, 1H), 8.02 (d, J=9.1 Hz, 1H), 6.60 (s, 1H), 5.10 (t, J=5.5 Hz, 1H), 4.55 (t, J=6.3 Hz, 2H), 3.78-3.73 (m, 2H) and 1.49 (s, 9H) ppm.
Workup
- customThe reaction mixture was partitioned between ethyl acetate and water
- washThe aqueous layer was washed with ethyl acetate
- washthe combined ethyl acetate layers were washed with water (×3) and brine
- dry with materialdried over MgSO4
- concentrationconcentrated
- customThe residue was purified by column chromatography (50-100% CH2Cl2-Hexanes)
Sources & evidence
- ORD record
- ord-593f0843e45d4ddf8ca2b9034dfcf045
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08623905B2
Reaction notes
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