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

https://huagongshe.com/de/reaction/417554

Beteiligte Stoffe

Rolle	Name	HCID	Einwaage
Edukt	Hydrochloric Acid	HCID 313	—
Edukt	Diisopropylethylamine	HCID 81531	—
Edukt	1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-	HCID 85083	—
Edukt	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Edukt	4-Bromo-4'-t-butoxycarbonylaminobiphenyl	HCID 59610534	—
Lösungsmittel	Methanol	HCID 887	—
Lösungsmittel	Dimethylformamide	HCID 6228	—
Lösungsmittel	Ethyl Acetate	HCID 8857	—
Produkt	2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66621324	95,2%

Reaktionsbedingungen

Temperatur	60 °C

Reaktionsschritte

(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).

Herkunft & Nachweise

DOI	10.6084/m9.figshare.5104873.v1
Patentnummer	US08088368B2
Quelldatensatz	uspto-grants-2012_01
ORD ID	ord-73403ab86f91493a93d84a27e482d755
Quellennotiz	uspto-grants-2012_01