Lithium hydroxide, monohydrate → 7,8-Dihydro-2,3-bis(4-methylphenyl)pyrido[2,3-b]pyrazine-5(6H)-heptanoic acid

온도

50 °C

Ethyl 7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (step 1) was dissolved in THF (94 ml) and lithium hydroxide monohydrate (7.79 g, 186 mmol) in water (94 ml) was added dropwise. The reaction mixture was warmed to 50° C. and stirred for 7.5 hours. The reaction mixture was concentrated in vacuo to remove the THF and diluted with water (500 ml). The pH of the aqueous layer was adjusted to pH 2 with 1 N HCl (100 ml) and extracted with EtOAc (3×500 ml). The combined organic layers were washed with brine (200 ml), dried over anhydrous sodium sulfate and concentrated in vacuo. The crude solid was suspended in TBME/hexane (1:1, 100 ml) and rotated on the rotary evaporator (no vacuum) at RT until crystals formed. The solid was removed by filtration, washed with heptane (50 ml) and dried at RT overnight. The solid was re-crystallized from a hot mixture of EtOH (211 ml) and water (159 ml). After seeding and stirring for 1 h at 5° C., the crystals were filtered off and the product dried overnight at 40° C. in a vacuum oven to afford the title compound;

1. concentrationThe reaction mixture was concentrated in vacuo
2. customto remove the THF
3. additiondiluted with water (500 ml)
4. extractionextracted with EtOAc (3×500 ml)
5. washThe combined organic layers were washed with brine (200 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customrotated on the rotary evaporator (no vacuum) at RT until crystals
9. customformed
10. customThe solid was removed by filtration
11. washwashed with heptane (50 ml)
12. customdried at RT overnight
13. customThe solid was re-crystallized from a hot mixture of EtOH (211 ml) and water (159 ml)
14. stirringstirring for 1 h at 5° C.
15. filtrationthe crystals were filtered off
16. customthe product dried overnight at 40° C. in a vacuum oven

ORD 기록

ord-89c353fced434f419c24d485e550dd98

출처 데이터셋

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09174985B2