Hydrochloric Acid → (2,4-Difluoro-3-formyl-phenyl)-carbamic acid methyl ester

Temperature

-78 °C

Into a reaction flask under nitrogen, diisopropylamine (24.87 g, 250 mmol) is combined with 160 mL of anhydrous tetrahydrofuran and the solution is cooled to −78° C. n-Butyllithium (154 mL, 1.6 M in hexanes, 250 mmol) is added dropwise, maintaining the temperature below −70° C. After stirring at −78° C. for 1 hour, (2,4-difluoro-phenyl)-carbamic acid methyl ester (2, 20.00 g, 110 mmol) in 40 mL of tetrahydrofuran is added dropwise, maintaining the temperature below −70° C. The reaction is stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 1 minute. The reaction is poured into 250 mL of water, the pH is adjusted to 1 with addition of 2M hydrochloric acid, and the mixture is extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried in hexane and the resulting solid is collected by filtration and dried to provide the desired compound (3, 19.38 g, 84%).

1. additionis added dropwise
2. temperaturemaintaining the temperature below −70° C
3. temperaturemaintaining the temperature below −70° C
4. stirringThe reaction is stirred at −78° C. for 1 hour
5. temperaturewarmed to room temperature
6. stirringstirred for 1 minute
7. extractionthe mixture is extracted with 3×250 mL of ethyl acetate
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationthe filtrate concentrated under vacuum
11. filtrationthe resulting solid is collected by filtration
12. customdried

ORD record

ord-55acc11c09b54ad8b912c6944ff5d368

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440969B2