Formaldehyde → t-Butyl 4-(5-formyl-4-hydroxypyridin-2-yl)piperazine-1-carboxylate

To a mixture of t-butyl 4-(4-hydroxypyridin-2-yl)piperazine-1-carboxylate (5.03 g, 18.0 mmol) and MgCl2 (3.42 g, 36 mmol) in CH3CN (100 mL) was added triethylamine (15.1 mL, 90 mmol). After the mixture was stirred for 10 minutes at ambient temperature, paraformaldehyde (5.4 g, 180 mmol) was added to the mixture. The mixture was stirred for 18 hours at 60° C., and then cooled to room temperature. The mixture was then diluted with EtOAc (400 mL) and washed with 1 M Rochelle salt solution (200 mL) and saturated NH4Cl solution (200 mL). The organic layer was concentrated under the reduced pressure and purified by column chromatography (30%-80% EtOAc/hexanes) to yield 1.5 g (27%) of t-butyl 4-(5-formyl-4-hydroxypyridin-2-yl)piperazine-1-carboxylate as white solid. MS m/z 308.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ (ppm) 11.37 (1H, s), 9.64 (1H, s), 8.27 (1H, s), 5.98 (1H, s), 3.71 (4H, m), 3.56 (4H, m), 1.48 (9H, s).

1. stirringThe mixture was stirred for 18 hours at 60° C.
2. temperaturecooled to room temperature
3. washwashed with 1 M Rochelle salt solution (200 mL) and saturated NH4Cl solution (200 mL)
4. concentrationThe organic layer was concentrated under the reduced pressure
5. custompurified by column chromatography (30%-80% EtOAc/hexanes)

ORDレコード

ord-a912fa74148b4360bf77dcb4cdb0eb6e

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09371336B2