Methyl iodide → 1,1-Dimethylethyl N-(2-fluoro-6-methylphenyl)carbamate

Temperature

-15 °C

A solution of tert-butyl 2-fluorophenylcarbamate (99.5 g, 471 mmol) in anhydrous tetrahydrofuran (900 mL) was placed under a nitrogen atmosphere, cooled in a dry ice-acetone bath, and stirred while t-butyllithium (666 mL of a 1.7M solution in pentane, 1132 mmol) was added slowly. The resulting mixture was slowly warmed up to −15° C. in 2 hours, then cooled back to −78° C. and treated with iodomethane (32.3 mL, 518 mmol). After warming up to −15° C. in 30 minutes, the mixture was removed from the cooling bath and treated with aqueous saturated NH4Cl (20 mL). The resulting slurry was diluted with CH2Cl2 (2000 mL), dried over MgSO4, filtered through a pad of silica, and concentrated under vacuum to afford tert-butyl 2-fluoro-6-methylphenylcarbamate(105 g, 99.5%) as a yellow solid.

1. temperaturecooled in a dry ice-acetone bath
2. additionwas added slowly
3. temperaturecooled back to −78° C.
4. temperatureAfter warming up to −15° C. in 30 minutes
5. customthe mixture was removed from the cooling bath
6. additiontreated with aqueous saturated NH4Cl (20 mL)
7. additionThe resulting slurry was diluted with CH2Cl2 (2000 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered through a pad of silica
10. concentrationconcentrated under vacuum

ORD record

ord-a7b1be70fac94c47b993e07ccf94025c

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157604B2