Potassium Phosphate, Tribasic → 2-(3-(quinolin-2-yl)phenoxy)-9H-carbazole

HRID 1509638Notes

Reaction equation

[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=1.I[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N+:31]([O-])=O)=[CH:21][CH:20]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.N1C=CC=CC=1C(O)=O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[CH:12]=[C:13]([CH:14]=[CH:15][CH:16]=1)[O:17][C:19]1[CH:24]=[CH:23][C:22]2[C:25]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[NH:31][C:21]=2[CH:20]=1

Participants

Conditions

Temperature: 85 °C

Procedure

3-(quinolin-2-yl)phenol (3.68 g, 15.30 mmol, 1.0 eq), 4′-iodo-2-nitrobiphenyl (5.97 g, 18.36 mmol, 1.2 eq), CuI (0.15 g, 0.77 mmol, 0.05 eq), picolinic acid (0.19 g, 1.53 mmol, 0.1 eq) and K3PO4 (6.50 g, 30.60 mmol, 2.0 eq) were added to a dry pressure vessel equipped with a magnetic stir bar. The vessel was evacuated and back-filled with nitrogen. The evacuation and back-fill procedure was repeated twice. Then solvent DMSO (32 mL) was added under nitrogen. After bubbling with nitrogen for 20 minutes, the mixture was heated to 80-90° C. in an oil bath. The reaction was monitored by TLC and about 22 hours later the starting material 3-(quinolin-2-yl)phenol was consumed completely. Then the mixture was cooled to ambient temperature and diluted with water, extracted with ethyl acetate three times. The combined organic layer was washed with water three times and dried over sodium sulfate, and filtered and washed with ethyl acetate. The filtrate was concentrated and the residue was purified through column chromatography on silica gel using hexane and ethyl acetate (10:1-5:1-3:1) as an eluent to obtain the desired product as a sticky brown liquid (5.98 g), which was used directly for the next step. A solution of PPh3 (11.19 g, 42.6 mmol) and the sticky brown liquid (5.95 g) obtained in the last step in 1,2-dichlorobenzene (28.4 mL) was stirred at a temperature of 175-185° C. in oil bath and for 21 hours under nitrogen, cooled and the solvent was removed by distillation under high vacuum. The residue was purified through column chromatography on silica gel using hexane and ethyl acetate (10:1-5:1-3:1) as an eluent to obtain the desired product 2-(3-(quinolin-2-yl)phenoxy)-9H-carbazole, which was further purified through recrystallization in ethyl acetate and hexane to get pure product as a white solid (4.45 g) in 75% total yield for the four steps. 1H NMR (DMSO-d6, 400 MHz): δ 6.96 (dd, J=8.4, 2.4 Hz, 1H), 7.13 (d, J=2.4 Hz, 1H), 7.16 (d, J=7.6 Hz, 1H), 7.21 (dd, J=8.4, 2.4 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.57-7.61 (m, 2H), 7.74-7.77 (m, 1H), 7.99-8.03 (m, 3H), 8.05-8.09 (m, 2H), 8.14 (d, J=5.6 Hz, 1H), 8.16 (d, J=5.2 Hz, 1H), 8.46 (d, J=9.2 Hz, 1H), 11.23 (s, 1H).

Workup

customequipped with a magnetic stir bar
customThe vessel was evacuated
additionback-filled with nitrogen
additionThen solvent DMSO (32 mL) was added under nitrogen
customAfter bubbling with nitrogen for 20 minutes
customwas monitored by TLC and about 22 hours
customwas consumed completely
temperatureThen the mixture was cooled to ambient temperature
additiondiluted with water
extractionextracted with ethyl acetate three times
washThe combined organic layer was washed with water three times
dry with materialdried over sodium sulfate
filtrationfiltered
washwashed with ethyl acetate
concentrationThe filtrate was concentrated
customthe residue was purified through column chromatography on silica gel

Sources & evidence

ORD record: ord-b800ddcac8654a2c9d58f361aa623655
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09224963B2

Reaction notes

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