Reaction #40276

Reaction equation

tert-butyl acetate

compound

5-(2,2-dimethyl-propionylamino)-pyrazine-2-carboxylic acid methyl ester

lithium bis(trimethylsilyl)amide

→

3-[5-(2,2-dimethylpropionylamino)-pyrazin-2-yl]-3-oxo-propionic acid-tert-butyl ester

Solvents

THF

THF

Conditions

Workup

1. 1
   OtherA 3-necked 1-L round bottomed flask equipped with a magnetic stirrer, addition funnel
2. 2
   Temperaturewhile maintaining the temperature of the reaction mixture between −20° C. and 0° C
3. 3
   Otherreaction
4. 4
   Temperatureto warm to 0° C.
5. 5
   Otherquenched by the addition of pre-cooled 200 mL (260.3 mmol) of 25 wt % citric acid solution
6. 6
   OtherThe organic layer was separated
7. 7
   Washwashed with 2×200 mL of saturated sodium chloride solution
8. 8
   Concentrationconcentrated at 30° C./60 mmHg to a volume of ca. 50 mL
9. 9
   workup.ADDITIONThe concentrated solution was diluted with 200 mL of butanone
10. 10
    Concentrationagain concentrated at 30° C./60 mmHg to ca. 50 mL
11. 11
    workup.ADDITIONThe concentrate was again diluted with 200 mL of butanone
12. 12
    Concentrationconcentrated at 30° C./60 mmHg to a volume of ca. 100 mL

Procedure

A 3-necked 1-L round bottomed flask equipped with a magnetic stirrer, addition funnel, thermocouple probe and nitrogen inlet/outlet was charged with 25.00 mL (185.5 mmol) of tert-butyl acetate, 20.00 g (84.30 mmol) of the compound prepared in step 2 and 20 mL of THF. After cooling to −20° C., a solution of 261.4 mL (261.4 mmol) of 10M lithium bis(trimethylsilyl)amide (LHMDS) in THF was added dropwise, while maintaining the temperature of the reaction mixture between −20° C. and 0° C. The resulting red solution was stirred at −20° C. for 40 min. HPLC analysis indicated complete reaction. The mixture was allowed to warm to 0° C., then quenched by the addition of pre-cooled 200 mL (260.3 mmol) of 25 wt % citric acid solution. The organic layer was separated, washed with 2×200 mL of saturated sodium chloride solution and concentrated at 30° C./60 mmHg to a volume of ca. 50 mL. The concentrated solution was diluted with 200 mL of butanone and again concentrated at 30° C./60 mmHg to ca. 50 mL. The concentrate was again diluted with 200 mL of butanone and concentrated at 30° C./60 mmHg to a volume of ca. 100 mL. NMR analysis indicated the absence of THF. The resulting butanone solution of the title compound was used directly in the next step.

Source