Ethyl Methanesulfonate → HCID 57750913, compound

Temperature

-78 °C

Ethyl methanesulfonate (1.00 mL, 9.34 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) in an oven dried round bottle under an atmosphere of argon. The solution was cooled to −78° C. and 2.5 M n-butyllithium in hexane (4.09 mL, 10.23 mmol) was added dropwise over 15 min. The mixture was stirred at −78° C. for 15 min and diethyl chlorophosphate (0.78 mL, 5.38 mmol) was added dropwise. The reaction was stirred at −78° C. for 1 h and then the temperature was allowed to reach 0° C. before recooling to −78° C. A solution of 2-bromo-5-formylpyridine (1.0 g, 5.38 mmol) in anhydrous tetrahydrofuran (5 mL) was added dropwise over 15 min and the resulting mixture was stirred for 15 min and then allowed to reach ambient temperature. Water (3 mL) was added and the solvent was evaporated in vacuo. The residue was partitioned between diethyl ether and water. The aqueous phase was extracted with diethyl ether and the formed precipitate was filtered off and rinsed with diethyl ether. This was pure product which was pooled with the rest of the material after purification. The aqueous phase was extracted once more with diethyl ether and the combined organic phases were dried over magnesium sulfate and concentrated. Purification by column chromatography, using a gradient of 10-60% ethyl acetate in heptane as the eluent, gave 0.77 g pooled with the material from the extractive work up to give 1.42 g (90% yield) of the title compound.

1. customdried round bottle under an atmosphere of argon
2. stirringThe reaction was stirred at −78° C. for 1 h
3. customto reach 0° C.
4. custombefore recooling to −78° C
5. stirringthe resulting mixture was stirred for 15 min
6. customto reach ambient temperature
7. customthe solvent was evaporated in vacuo
8. customThe residue was partitioned between diethyl ether and water
9. extractionThe aqueous phase was extracted with diethyl ether
10. filtrationthe formed precipitate was filtered off
11. washrinsed with diethyl ether
12. customafter purification
13. extractionThe aqueous phase was extracted once more with diethyl ether
14. dry with materialthe combined organic phases were dried over magnesium sulfate
15. concentrationconcentrated
16. customPurification by column chromatography
17. customgave 0.77 g

ORD record

ord-febf2b8a51654e01a800e6e3ce8499f9

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145380B2