Nitrogen → 6-[3-(2-Chloro-3,6-difluoro-phenyl)isoxazol-5-ylmethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic Acid 1'-tert-butyl Ester 3'-ethyl Ester

関与物質

役割	名称	HCID	仕込み量
反応物	Nitrogen	HCID 947	—
反応物	Sodium Carbonate	HCID 10340	—
反応物	1-(tert-Butyl) 3-ethyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1,3(2H)-dicarboxylate	HCID 22228409	—
反応物	2-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine	HCID 67148796	—
触媒	HCID 178418397	HCID 178418397	—
溶媒	1,2-Dimethoxyethane	HCID 8071	—
溶媒	Ethyl Acetate	HCID 8857	—
生成物	6-[3-(2-Chloro-3,6-difluoro-phenyl)isoxazol-5-ylmethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic Acid 1'-tert-butyl Ester 3'-ethyl Ester	HCID 67148985	62.2%

反応条件

温度	80 °C

反応手順

Compound A2 (9.52 g, 23.6 mmol) and 2-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (13.2 g, 29.5 mmol) were dissolved in DME (164 mL), and aq. 2M Na2CO3 (118 mL) was added. The mixture was degassed with N2 (5 min), and Pd(PPh3)4 (1.36 g, 1.18 mmol) was added. The mixture was heated rapidly to 80° C., and was stirred at this temperature for 1 h. The mixture was allowed to cool to rt, and was diluted with EtOAc (200 mL). The mixture was washed with water (200 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane→EtOAc/heptane 30:70) yielded the title compound (8.45 g, 62%). LC-MS: tR=1.13 min, ES+: 576.41.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US07968720B2
出典データセット	uspto-grants-2011_06
ORD ID	ord-7e9dca83f617441ea03c8f72561a3acb
出典メモ	uspto-grants-2011_06