Sulfuric Acid → (E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](O)([CH3:25])[CH2:9][N:10]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]3[CH2:20][N:21]([CH3:24])[CH2:22][CH2:23][C:11]2=3)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[F:1][C:2]1[CH:3]=[CH:4][C:5](/[C:8](/[CH3:25])=[CH:9]/[N:10]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]3[CH2:20][N:21]([CH3:24])[CH2:22][CH2:23][C:11]2=3)=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 2.5 °C
Procedure
2-(4-fluorophenyl)-1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propan-2-ol (4.6 g, 13.05 mmol, 1 equiv.) was heated to reflux with 25% aqueous sulfuric acid (14 mL) for 2 h. The reaction mixture was cooled to 0-5° C. and made alkaline with 15% aqueous KOH solution and extracted with THF:EtOAc (1:1 mixture, 2×30 mL). The combined organic layer was washed with water (15 mL) and brine, dried over sodium sulfate and evaporated under vacuum to obtain the crude product that was purified by flash chromatography on silica gel using EtOAc as eluent. 1H NMR (DMSO-d6, oxalate salt) δ (ppm): 10.0 (bs, 1H), 7.7 (m, 2H), 7.2 (m, 3H), 7.10 (d, 2H), 7.0 (d, 1H), 4.6 (d, 1H), 4.3 (d, 1H), 3.7 (bs, 1H), 3.49 (bs, 1H), 3.0 (bs, 2H), 3.0 (s, 3H), 2.4 (s, 3H), 1.8 (s, 3H).
Workup
- extractionextracted with THF:EtOAc (1:1 mixture, 2×30 mL)
- washThe combined organic layer was washed with water (15 mL) and brine
- dry with materialdried over sodium sulfate
- customevaporated under vacuum
Sources & evidence
- ORD record
- ord-a4bc222489eb4dbba1a6a2fad961d79c
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08906925B2
Reaction notes
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