Tetrahydrofuran → Ethanol heptane

Temperature

1 °C

13.94 g of 2-amino-5-chloropyridine (1.5 equiv.) and 30 g mono ester mono amide (70.85 mmol, 1 equiv.) were dissolved in 240 ml THF. The solution was cooled to 0-2° C. and 212.6 ml 1M LiHMDS solution in THF (3 equiv.) was added over 20 min. After 1.5 h reaction (in process control by HPLC), 245 ml 2M HClaq were added over 15 min keeping the temperature between 0-10° C. (pH of resulting mixture: 3.2). The resulting mixture was extracted twice with 350 ml ethyl acetate. The organic phases were washed sequentially with 200 ml half saturated NaClaq, combined, dried over Na2SO4, filtered and concentrated under reduced pressure to give crude product which was then purified by crystallized from a 1:2 ethanol/heptane mixture (85% yield).

1. customAfter 1.5 h reaction (in process control by HPLC), 245 ml 2M HClaq
2. additionwere added over 15 min
3. custombetween 0-10° C.
4. custom(pH of resulting mixture: 3.2)
5. extractionThe resulting mixture was extracted twice with 350 ml ethyl acetate
6. washThe organic phases were washed sequentially with 200 ml half saturated NaClaq
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto give crude product which
11. customwas then purified

ORD record

ord-043d43e9806748e5b339101ea8412309

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07872141B2