Cesium carbonate → 1'-Butyl-3'-chloro-4-hydroxymethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4]bipyridinyl-2'-one

関与物質

役割	名称	HCID	仕込み量
反応物	Cesium carbonate	HCID 10796	—
反応物	4-Phenylpiperidine-4-methanol	HCID 77896	—
反応物	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
反応物	Trifluoromethanesulfonic acid 1-butyl-3-chloro-2-oxo-1,2-dihydropyridin-4-yl ester	HCID 25221428	—
触媒	palladium(II) acetate	HCID 167845	—
溶媒	Water	HCID 962	—
溶媒	Dichloromethane	HCID 6344	—
溶媒	(Trifluoromethyl)benzene	HCID 7368	—
生成物	1'-Butyl-3'-chloro-4-hydroxymethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4]bipyridinyl-2'-one	HCID 59497081	—

反応条件

温度	100 °C

反応手順

4-Hydroxymethyl-4-phenylpiperidine (0.172 g, 0.9 mmol), palladium(II) acetate (0.007 g, 0.03 mmol), cesium carbonate (0.391 g, 1.2 mmol) and Xantphos (0.035 g, 0.06 mmol) were added to a solution of intermediate D9 (0.2 g, 0.6 mmol) in trifluoromethylbenzene (2 ml). The reaction mixture was heated at 100° C. for 24 hours in a sealed tube, after which it was cooled to room temperature. Subsequently, it was diluted with DCM, H2O (5 ml) and extracted with EtOAc (3×5 ml). The mixture was filtered through diatomaceous earth, and the filtrate was evaporated to dryness. The crude product was purified first by column chromatography (silica gel; eluent: DCM/EtOAc from 90/10 to 0/100) and then by reversed phase HPLC. The desired fractions were collected, evaporated in vacuo and finally freeze dried to yield compound E22 (0.041 g, 18%) as a white foam.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US09132122B2
出典データセット	uspto-grants-2015_09
ORD ID	ord-bf136c5a63294f01ab1c6c0a8b5a03e7
出典メモ	uspto-grants-2015_09