Chlorotrimethylsilane → 4-Chloro-2-methoxyimino-3-oxobutanoic acid

Temperature

-30 °C

In 15 ml of acetonitrile was dissolved 725 mg of 2-methoxyimino-3-oxobutyric acid, followed by addition of 2.8 ml of triethylamine. Then, 2.5 ml of chlorotrimethylsilane was added dropwise with ice-cooling and the mixture was stirred at 20°-25° C. for 2 hours. After addition of 10 ml of xylene, the reaction mixture was concentrated under reduced pressure and the residue was suspended in 15 ml of tetrahydrofuran. The suspension was filtered in a nitrogen gas stream to remove insolubles. This filtrate containing trimethylsilyl 2-ethoxyimino-3-oxobutyrate trimethylsilyl enol ether (i.e. trimethylsilyl 2-methoxyimino-3-trimethylsilyloxy-3-butenoate) was cooled to -30° C. and 0.45 ml of sulfuryl chloride was added dropwise thereto. After the temperature of the mixture was increased to 20° C., the reaction mixture was concentrated under reduced pressure and the residue was diluted with 20 ml of water and stirred for 10 minutes for hydrolyzing the trimethylsilyl ester. Then, 2N aqueous sodium hydroxide solution was added dropwise to adjust the reaction mixture to pH 9.0. The reaction mixture was washed twice with 20 ml portions of methylene chloride and the aqueous layer was adjusted to pH 0.5 by dropwise addition of concentrated hydrochloric acid. The aqueous layer was saturated with sodium chloride and extracted 3 times with 20 ml portions of ether. The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The above procedure gave 4-chloro-2-methoxyimino-3-oxobutyric acid.

1. temperaturecooling
2. concentrationthe reaction mixture was concentrated under reduced pressure
3. filtrationThe suspension was filtered in a nitrogen gas stream
4. customto remove insolubles
5. additionThis filtrate containing trimethylsilyl 2-ethoxyimino-3-oxobutyrate trimethylsilyl enol ether (i.e. trimethylsilyl 2-methoxyimino-3-trimethylsilyloxy-3-butenoate)
6. addition0.45 ml of sulfuryl chloride was added dropwise
7. temperatureAfter the temperature of the mixture was increased to 20° C.
8. concentrationthe reaction mixture was concentrated under reduced pressure
9. additionthe residue was diluted with 20 ml of water
10. stirringstirred for 10 minutes
11. additionThen, 2N aqueous sodium hydroxide solution was added dropwise
12. washThe reaction mixture was washed twice with 20 ml portions of methylene chloride
13. additionthe aqueous layer was adjusted to pH 0.5 by dropwise addition of concentrated hydrochloric acid
14. extractionextracted 3 times with 20 ml portions of ether
15. dry with materialdried over anhydrous magnesium sulfate
16. concentrationconcentrated under reduced pressure

ORD record

ord-fa38fb39e9654007af6adf6bb35a2395

Source dataset

uspto-grants-1989_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04845257