Sodium Carbonate → HCID 54596515, compound

Temperature

100 °C

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with 155n (312 mg, 0.931 mmol), 118f (472 mg, 1.12 mmol), sodium carbonate (296 mg, 2.79 mmol), DMF (2 mL), water (2 mL) and 1,4-dioxane (10 mL). After bubbling nitrogen through the resulting suspension for 30 min, tetrakis-(triphenylphosphine)palladium(0) (215 mg, 0.186 mmol) was added. A reflux condenser was attached to the flask, and the reaction mixture was heated at 100° C. for 14 h. After this time, the mixture was diluted with 90:10 methylene chloride/methanol (100 mL) and water (75 mL), and the layers were separated. The aqueous layer was extracted with 90:10 methylene chloride/methanol (2×50 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was dissolved in a mixture of THF (5 mL), water (5 mL) and methanol (5 mL). Lithium hydroxide monohydrate (195 mg, 4.66 mmol) was added, and the mixture was stirred at room temperature for 3 h. After this time, the mixture was diluted with 90:10 methylene chloride/methanol (100 mL) and water (50 mL), and the layers were separated. The aqueous layer was extracted with 90:10 methylene chloride/methanol (2×75 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, 90:10 methylene chloride/methanol) to afford 227 in 7% yield (36 mg) as an amorphous off-white solid: mp 227-229° C.; 1H NMR (500 MHz, DMSO-d6) d 8.66 (d, J=1.5 Hz, 1H), 8.53 (s, 1H), 8.11 (s, 1H), 7.68 (d, J=7.0 Hz, 1H), 7.44 (t, J=8.0 Hz, 1H), 7.39 (s, 1H), 7.29 (m, 3H), 6.01 (s, 1H), 4.72 (t, J=4.5 Hz, 1H), 4.33 (s, 2H), 3.99-3.88 (m, 3H), 3.84-3.75 (m, 2H), 3.59 (m, 3H), 3.51 (m, 5H), 3.02-2.91 (m, 2H), 2.72 (t, J=5.5 Hz, 2H), 1.92 (t, J=5.0 Hz, 2H), 1.77-1.73 (m, 2H); MS (ESI+) m/z 551.2 (M+H).

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
2. customAfter bubbling nitrogen through the resulting suspension for 30 min
3. customA reflux condenser was attached to the flask
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with 90:10 methylene chloride/methanol (2×50 mL)
6. washthe combined organic layers were washed with brine (100 mL)
7. dry with materialdried over sodium sulfate
8. customThe drying agent was removed by filtration
9. concentrationThe filtrate was concentrated under reduced pressure
10. dissolutionthe resulting residue was dissolved in a mixture of THF (5 mL), water (5 mL) and methanol (5 mL)
11. customthe layers were separated
12. extractionThe aqueous layer was extracted with 90:10 methylene chloride/methanol (2×75 mL)
13. washthe combined organic layers were washed with brine (100 mL)
14. dry with materialdried over sodium sulfate
15. customThe drying agent was removed by filtration
16. concentrationThe filtrate was concentrated under reduced pressure
17. customthe resulting residue was purified by flash column chromatography (silica, 90:10 methylene chloride/methanol)

ORD record

ord-ebe96fdeff2140d5b4d5f1bab560f9d6

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618107B2