Hydrochloric Acid → 2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

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	1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-	HCID 85083	—
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	4-Bromo-4'-t-butoxycarbonylaminobiphenyl	HCID 59610534	—
溶媒	Methanol	HCID 887	—
溶媒	Dimethylformamide	HCID 6228	—
溶媒	Ethyl Acetate	HCID 8857	—
生成物	2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66621324	95.2%

反応条件

温度	60 °C

反応手順

(4′-Bromo-biphenyl-4-yl)-carbamic acid tert-butyl ester (407 mg, 1.17 mmol) was dissolved in methanol (10 mL) and concentrated HCl (2 mL) was added. The solution was stirred at 60° C. for 1 hour then concentrated. The crude residue was treated with Boc-Pro-OH (302 mg, 1.40 mmol) and HATU (578 mg, 1.52 mmol) and suspended in DMF (6 mL). DIPEA (1.02 mL, 5.85 mmol) was added and the reaction mixture was stirred at RT for 4 hours after which it was diluted with ethyl acetate (200 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The residue was purified by silica column chromatography (30% to 55% EtOAc/hexanes) to afford 2-(4′-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (496 mg, 95% over 2 steps).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08822430B2
出典データセット	uspto-grants-2014_09
ORD ID	ord-dd81dafd00634a3ba3e3b2423110c4c3
出典メモ	uspto-grants-2014_09