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

참여 물질

역할	이름	HCID	투입량
반응물	Hydrochloric Acid	HCID 313	—
반응물	Diisopropylethylamine	HCID 81531	—
반응물	1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-	HCID 85083	—
반응물	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
반응물	4-Bromo-4'-t-butoxycarbonylaminobiphenyl	HCID 59610534	—
용매	Methanol	HCID 887	—
용매	Dimethylformamide	HCID 6228	—
용매	Ethyl Acetate	HCID 8857	—
생성물	2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66621324	95.2%

반응 조건

온도	60 °C

반응 단계

(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).

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US08822430B2
출처 데이터셋	uspto-grants-2014_09
ORD ID	ord-dd81dafd00634a3ba3e3b2423110c4c3
출처 메모	uspto-grants-2014_09