Dimethyl Sulfoxide → 4-[2-(3-Naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-2-en-8-yl)-ethoxy]-1H-indole

HRID 987565Notes

Reaction equation

Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH:7]=[CH:8][NH:9]2.[CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][C:15]=1[C:24]1[CH2:30][CH:29]2[NH:31][CH:26]([CH2:27][CH2:28]2)[CH:25]=1.CS(C)=O>O>[CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][C:15]=1[C:24]1[CH2:25][CH:26]2[N:31]([CH2:2][CH2:3][O:4][C:5]3[CH:13]=[CH:12][CH:11]=[C:10]4[C:6]=3[CH:7]=[CH:8][NH:9]4)[CH:29]([CH2:28][CH2:27]2)[CH:30]=1

Participants

Conditions

Temperature: 23 °C

Procedure

4-(2-Chloro-ethoxy)-1H-indole (170 mg, 0.87 mmol), 469 mg (1.74 mmol) of 3-naphthalen-2-yl-8-aza-bicyclo[3.2.1]oct-2-ene and 10 mL of DMSO are heated at 100° C. for 24 h. After cooling to 23° C., the orange reaction mixture is poured into 100 mL H2O. Extraction with CH2Cl2 (2×50 mL), combining the organic layers and washing with H2O (4×50 mL), brine (1×50 mL), drying over MgSO4, and evaporation gives an orange oil. Flash chromatography on SiO2 gel, eluting with CHCl3/MeOH (40/1 to 10/1), gives 216 mg (0.59 mmol, a 63% yield) of the title compound as an off-white solid. The corresponding oxalate salt is prepared by combining the title compound with 1 equiv. of oxalic acid in EtOH. A white solid precipitates. Recrystallization from EtOH/Et2O gives the oxalate salt of the title compound as an off-white solid. mp: 212-215° C.; MS (ES) m/z 395 (MH)+.

Workup

extractionExtraction with CH2Cl2 (2×50 mL)
washwashing with H2O (4×50 mL), brine (1×50 mL)
dry with materialdrying over MgSO4, and evaporation
customgives an orange oil
washFlash chromatography on SiO2 gel, eluting with CHCl3/MeOH (40/1 to 10/1)
customgives 216 mg (0.59 mmol

Sources & evidence

ORD record: ord-b0edbd1ba6204a7ea6ec6f6debbff642
Source dataset: uspto-grants-2003_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06632824B2

Reaction notes

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