Chlorotrimethylsilane → (+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate

Temperature

-20 °C

To a 500 mL, 3-neck round bottom flask equipped with a mechanical stirrer and under a blanket of nitrogen was charged 110 mL of lithium bis(trimethylsilyl)amide (1.0M solution in THF) while maintaining the internal temperature at -20° C. using an isopropanol/dry ice bath. Once the desired temperature was attained, 20.14 g of 3-(trimethylsilyl)-2-propynal (a 62.7% solution in MTBE) was added to the reaction flask over 2 h. Upon completing the addition, the reaction mixture was stirred for 10 min at -20° C. followed by the addition of 10.3 g of trimethyl silyl chloride over a period of 20 min while maintaining the batch temperature at -20° C. Upon completing the addition the reaction mixture was stirred for 10 min at which time 69.7 g of t-butyl acetate was added to the reaction mixture over 15 min while maintaining the batch temperature at -20° C. The reaction mixture was stirred for 10 min at -20° C. at which time 19.2 mL of lithium bis(trimethylsilyl)amide (1.0M solution in THF) was added over a period of 40 min while maintaining the batch temperature at -20° C. An in-process check was performed on an aliquot using GC Method C to ensure that the area % of the desired product was >55%. The reaction mixture was added to an ammonium chloride solution (prepared by adding 5.0 g of ammonium chloride in 25 mL of water) and the mixture was allowed to reach ambient temperature with stirring (25° C.). The mixture was stirred at ambient temperature (25° C.) for 1 h. The mixture was transferred to a separatory funnel and the phases were separated. An in-process check was performed using GC Method C to determine the presence of desired product. This material was used without further purification. The solvent from the organic phase was removed under reduced pressure to give 34.5 g of the title compound as a brown oil (49.52 wt %, a molar yield of 70.7%).

1. customTo a 500 mL, 3-neck round bottom flask equipped with a mechanical stirrer and under a blanket of nitrogen
2. additionthe addition
3. temperaturewhile maintaining the batch temperature at -20° C
4. additionthe addition the reaction mixture
5. additionwas added to the reaction mixture over 15 min
6. temperaturewhile maintaining the batch temperature at -20° C
7. additionwas added over a period of 40 min
8. temperaturewhile maintaining the batch temperature at -20° C

ORD record

ord-51f57e41c82d40279e4c1b4a9b0d5bcf

Source dataset

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05631399