Methanol → 3-(hydroxymethyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-6(6aH)-one

温度

-45 °C

Methyl 6-oxo-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-3-carboxylate (500 mg, 1.91 mmol) was taken up in tetrahydrofuran (23 mL) in an inert environment. To the stirred suspension at room temperature was added NaH (60% dispersion in mineral oil, 114.7 mg, 2.87 mmol) and stirred 30 min. The reaction was then cooled to −45° C. and lithium aluminum hydride (2M in THF, 1.91 mL, 3.82 mmol) was added. The reaction was stirred at a temperature between −20 and −10° C. for 1 h. The reaction was then cooled back to −60° C. and MeOH (1 mL) followed by water (1 mL) was added. The reaction was allowed to stir at ambient temperature for 2 h and then poured into ethyl acetate (300 mL) and water (200 mL). The biphasic mixture was stirred vigorously and then filtered through a medium frit. The layers were separated and the aqueous phase was extracted with ethyl acetate (3×100 mL). The organic layers were combined, washed with brine (100 mL), dried with sodium sulfate and concentrated to yield the title compound (429.4 mg, 96%) as a white solid. [M+H] calc'd for C12H15N3O2, 234; found, 234.

1. stirringThe reaction was stirred at a temperature between −20 and −10° C. for 1 h
2. temperatureThe reaction was then cooled back to −60° C.
3. additionwas added
4. stirringto stir at ambient temperature for 2 h
5. stirringThe biphasic mixture was stirred vigorously
6. filtrationfiltered through a medium frit
7. customThe layers were separated
8. extractionthe aqueous phase was extracted with ethyl acetate (3×100 mL)
9. washwashed with brine (100 mL)
10. dry with materialdried with sodium sulfate
11. concentrationconcentrated

ORDレコード

ord-b0dd60d38fa44ce499ed032f46d9674d

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08822470B2