Hydrochloric Acid → tert-butyl N-(6-chloro-3-formylpyridin-2-yl)carbamate

Temperature

-78 °C

The reaction apparatus was baked out, and the reaction was effected under argon and was stirred. 15 g (65.6 mmol) of tert-butyl (6-chloropyridin-2-yl)carbamate (Example 1A) and 19 g (164 mmol) of 1,2-bis(dimethylamino)ethane were initially charged in 270 ml of THF and cooled to −78° C. 102.5 ml (164 mmol) of butyllithium (1.6 N) were added dropwise. After the dropwise addition had ended, the reaction was warmed gradually to −10° C. and kept at −10° C. for 2 h. Then it was cooled again to −78° C., and 10 ml (131 mmol) of DMF were added. The reaction was warmed gradually to RT and the reaction mixture was added to 1 l of ethyl acetate and 350 ml of 1 N hydrochloric acid, the mixture was stirred for 15 min and the organic phase was removed. It was washed with water and saturated sodium hydrogencarbonate solution, dried over magnesium sulphate and concentrated on a rotary evaporator. The residue was admixed with diethyl ether, and the solids were filtered off with suction and dried. 12.3 g (73% of theory) of the product were obtained in solid form.

1. additionAfter the dropwise addition
2. temperaturethe reaction was warmed gradually to −10° C.
3. temperatureThen it was cooled again to −78° C.
4. temperatureThe reaction was warmed gradually to RT
5. stirringthe mixture was stirred for 15 min
6. customthe organic phase was removed
7. washIt was washed with water and saturated sodium hydrogencarbonate solution
8. dry with materialdried over magnesium sulphate
9. concentrationconcentrated on a rotary evaporator
10. filtrationthe solids were filtered off with suction
11. customdried
12. custom12.3 g (73% of theory) of the product were obtained in solid form

ORD record

ord-eabe131dfa9549d0ad4063a4cb88eb60

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664246B2