Methyl chloroformate → HCID 64534371, compound

Temperature

-78 °C

To a mixture of (diazomethyl)trimethylsilane (2.0 M in hexanes, 25 mL, 50 mmol) in tetrahydrofuran (100 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 20 mL, 50 mmol) over 5 minutes. After the addition was complete, the reaction mixture temperature was maintained at about −78° C. for 30 minutes and then 2,6-difluorobenzaldehyde (7.1 g, 50 mmol) was added portionwise. The reaction mixture was maintained at −78° C. for an additional 30 minutes and then allowed to warm to room temperature, during which time gas evolution occurred. The reaction mixture was again cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 28 mL, 70 mmol) was added over 5 minutes. After 15 minutes at −78° C., methyl chloroformate (7.8 mL, 100 mmol) was added to the reaction mixture. After 30 minutes, the reaction mixture was allowed to warm to 0° C., and then partitioned between diethyl ether and saturated ammonium chloride solution. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound (8.0 g).

1. additionAfter the addition
2. temperatureThe reaction mixture was maintained at −78° C. for an additional 30 minutes
3. temperatureto warm to room temperature, during which time gas evolution
4. temperatureThe reaction mixture was again cooled to −78° C.
5. waitAfter 30 minutes
6. temperatureto warm to 0° C.
7. custompartitioned between diethyl ether and saturated ammonium chloride solution
8. customThe organic phase was separated
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

ORD record

ord-472f9b8aa6644334a01096cfe00d3728

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09131693B2