Reaction #40280

Reaction equation

N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-2,2-dimethyl-propionamide

potassium carbonate

→

5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-ylamine

Yield 63.0%

Solvents

methanol

Conditions

Workup

1. 1
   OtherTherefore, the solvent was removed under reduced pressure at 25° C
2. 2
   ConcentrationThe resulting residue was again concentrated in vacuo from ethyl acetate (50 mL)
3. 3
   OtherThe material was purified
4. 4
   OtherThe early fractions collected
5. 5
   ConcentrationThe later fractions were concentrated in vacuo

Procedure

A mixture of N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-2,2-dimethyl-propionamide (8.4 g, 30.7 mmol) and potassium carbonate (4.32 g, 31.2 mmol) in methanol (150 mL) was stirred at 25° C. for 16.5 h, at which time, thin layer chromatography suggested partial conversion to a more polar product. In an effort to avoid epimerization at the stereogenic center, the reaction was discontinued before completion. Therefore, the solvent was removed under reduced pressure at 25° C. The resulting residue was again concentrated in vacuo from ethyl acetate (50 mL). The material was purified using Biotage chromatography (FLASH 40 L, Silica, ethyl acetate). The early fractions collected allowed for the recovery of unreacted starting pivaloylamide as a white solid (2.0 g, 24%). The later fractions were concentrated in vacuo to provide 5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-ylamine (3.7 g, 63%) as a pale yellow oil. High-performance liquid chromatography analysis with a chiral column indicated 100% ee.

Source