Hydrochloric Acid → (R)-Pyrrolidin-2-yl((R)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-yl)methanone

https://huagongshe.com/ja/reaction/445357

関与物質

役割	名称	HCID	仕込み量
反応物	Hydrochloric Acid	HCID 313	—
反応物	Diisopropylethylamine	HCID 81531	—
反応物	(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid	HCID 688022	—
反応物	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
反応物	(R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline	HCID 28293305	—
溶媒	Water	HCID 962	—
溶媒	Dimethylformamide	HCID 6228	—
溶媒	1,4-Dioxane	HCID 31275	—
生成物	(R)-Pyrrolidin-2-yl((R)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-yl)methanone	HCID 59536406	—

反応手順

To a stirred mixture of (R)-1-(tert-butoxy-carbonyl)pyrrolidine-2-carboxylic acid (0.078 g, 0.36 mmol), (R)-1-(4-(trifluoro-methyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.100 g, 0.36 mmol) and DIEA (0.047 g, 0.36 mmol) in DMF (2 mL) was added HATU (0.14 g, 0.36 mmol). The reaction mixture was continued to stir overnight at RT, hydrolyzed with H2O, extracted with DCM (3×), dried over Na2SO4, concentrated and purified by ISCO (20% EtOAc/hexanes) to give the white solid which was dissolved in p-dioxane (2 mL) and added 1 mL of 4M HCl in p-dioxane. The mixture was continued to stir at RT overnight, concentrated, taken up in H2O, and neutralized by saturated aqueous NaHCO3, and filtered the light yellow solid which was dried by air. MS (ESI, positive ion) m/z: 375 (M+1).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08476297B2
出典データセット	uspto-grants-2013_07
ORD ID	ord-9a93e900122a4fc9b1bab144aa9bc64f
出典メモ	uspto-grants-2013_07