Dimethylformamide → 3-(3-diethylaminopropyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1([CH3:24])[CH2:15][C:14]2[NH:13][CH:12]=[C:11]([CH2:16][CH2:17][CH2:18][N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])[C:10]=2[CH2:9][CH2:8]1.CN(C)[CH:27]=[O:28]>>[CH2:20]([N:19]([CH2:22][CH3:23])[CH2:18][CH2:17][CH2:16][C:11]1[C:10]2[CH2:9][CH2:8][C:7]([CH3:6])([CH3:24])[CH2:15][C:14]=2[NH:13][C:12]=1[CH:27]=[O:28])[CH3:21]Participants
Procedure
Phosphorus oxychloride (0.35 mL, 3.74 mmol) was added dropwise to cooled dimethylformamide (0.8 mL, 10.3 mmol). After stirring at room temperature for 30 minutes, the mixture was cooled to −5° C. and a solution of [3-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-propyl]-diethyl-amine (0.9 g, 3.4 mmol) in dimethylformamide (2 mL) was added dropwise. The mixture was stirred at room temperature for 3 hours. The reaction was quenched with ice, followed by 10 N potassium to adjust the pH to 10–11. After stirring at room temperature for 1 hour, the reaction was extracted with ethyl acetate and the extract was washed with brine, dried and concentrated to give 0.55 g of 3-(3-diethylamino-propyl)-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde. 1H-NMR (360 MHz, dimethylsulfoxide-d6) δ 11.23 (br, s, 1H, NH), 9.41 (s, 1H, CHO), 2.61 (t, 2H, CH2), 2.30–2.43 (m, 10 H, 5×CH2), 1.58 (m, 2H, CH2), 1.45 (t, 2H, CH2), 0.93 (s, 6H, 2×CH3), 0.89 (t, 6H, CH3). MS m/z 290 [M+].
Workup
- temperaturethe mixture was cooled to −5° C.
- stirringThe mixture was stirred at room temperature for 3 hours
- customThe reaction was quenched with ice
- stirringAfter stirring at room temperature for 1 hour
- extractionthe reaction was extracted with ethyl acetate
- washthe extract was washed with brine
- customdried
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-82b32ca1f94a4fd9b462501543763308
- Source dataset
- uspto-grants-2007_01
- Patent number
- US07157577B2
Reaction notes
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