Ammonium Chloride → 2-(6-Bromopyridin-2-yl)-2-morpholin-4-ylethanol

Temperature

-78 °C

To a solution of 4-[(6-bromopyridin-2-yl)methyl]morpholine (Example 2, Step 1) (500 mg, 1.945 mmol) in tetrahydrofuran at −78° C. was added a solution of LDA (1.8 M in tetrahydrofuran/heptane/ethylbenzene, 3.24 ml, 5.83 mmol) over 15 minutes. The resulting red solution was stirred at −78° C. for one hour and then a solution of 1H-1,2,3-benzotriazol-1-ylmethanol (580 mg, 3.89 mmol) in 14 mL tetrahydrofuran was added. After 2.5 hours, a saturated aqueous ammonium chloride solution (5 mL) was added and the reaction mixture was allowed to warm to room temperature. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried with sodium sulfate, filtered, and concentrated. The resulting oil was dissolved in tetrahydrofuran (15 mL) and diethyl ether (30 mL), and this solution was washed with aqueous sodium hydroxide (5 M, 15 mL), brine (15 mL), saturated aqueous sodium carbonate (10 mL), and brine (10 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated. The resulting material was purified by silica gel chromatography (0.2-10% methanol/ethyl acetate) which afforded the title compound. LRMS (APCI) calc'd for C11H15BrN2O2 [M+H]+: 287, Found: 287.

1. waitAfter 2.5 hours
2. temperatureto warm to room temperature
3. customThe layers were separated
4. washthe organic layer was washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL)
5. dry with materialdried with sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe resulting oil was dissolved in tetrahydrofuran (15 mL)
9. washdiethyl ether (30 mL), and this solution was washed with aqueous sodium hydroxide (5 M, 15 mL), brine (15 mL), saturated aqueous sodium carbonate (10 mL), and brine (10 mL)
10. dry with materialThe organic layer was dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe resulting material was purified by silica gel chromatography (0.2-10% methanol/ethyl acetate) which

ORD record

ord-25ed94e6dc4b40de85bac8dfd6f61777

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278335B2