Water → HCID 89486836, compound

Temperature

-40 °C

ethyl 2-(6-chloro-2-methylpyrimidin-4-yl)cyclopropanecarboxylate (4-2, 6.8 g, 28.3 mmol, 1.0 eq) was dissolved in THF (141 ml) and cooled to −40° C. with dry ice acetone bath. LAH (32.5 ml, 32.5 mmol, 1.2 eq) (1.0 M solution in THF) was added dropwise over 10 minutes. The reaction appeared complete. To the reaction mixture was added water at 0° C. as to not raise the internal reaction temperature above −10° C., followed by 15% aqueous sodium hydroxide solution (2 mL). The cooling bath was removed and additional water (6 mL) was added. The reaction mixture was stirred for 1 hour. The salts were filtered off through celite and the solid was washed with THF (5×20 mL). The filtrate was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (0-100% ethyl acetate in hexanes) to afford ((1R,2R)-2-(6-chloro-2-methylpyrimidin-4-yl)cyclopropyl)methanol (4-3).

1. temperatureraise the internal reaction temperature above −10° C.
2. customThe cooling bath was removed
3. additionadditional water (6 mL) was added
4. filtrationThe salts were filtered off through celite
5. washthe solid was washed with THF (5×20 mL)
6. dry with materialThe filtrate was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel column chromatography (0-100% ethyl acetate in hexanes)

ORD record

ord-a6067e415ac04650857bf38403e57608

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200001B2