Acetaldehyde → 1-(6-Bromopyridin-2-yl)-1-morpholin-4-ylpropan-2-ol

Temperature

-78 °C

4-[(6-Bromopyridin-2-yl)methyl]morpholine (Example 45, step 1) (200 mg, 0.78 mmol) was placed under argon and then taken up in tetrahydrofuran (8 mL). The solution was cooled to −78° C. followed by the addition of LDA (0.65 mL of 1.8 M, 1.17 mmol) over 30 minutes. The reaction was maintained at −78° C. for one hour. Acetaldehyde (0.1 mL, 7.8 mmol) was then added and the reaction was then stirred at −78° C. for 2 hours. An additional portion of acetaldehyde (0.1 mL, 7.8 mmol) was then added and the reaction was then stirred an additional 2 hrs at −78° C. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification of the crude mixture via flash chromatography (silica, 0-5% methanol/ethyl acetate) afforded the title compound as a white solid.

1. temperatureThe reaction was maintained at −78° C. for one hour
2. stirringthe reaction was then stirred an additional 2 hrs at −78° C
3. customThe reaction was quenched with water
4. extractionextracted with ethyl acetate
5. dry with materialThe organic layer was dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification of the crude mixture via flash chromatography (silica, 0-5% methanol/ethyl acetate)

ORD record

ord-85fcc155ce58477889730844c86a12c8

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367706B2