Hydrochloric Acid → rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((R)-3,4-dihydroxy-butyl)-amide

Beteiligte Stoffe

Rolle	Name	HCID	Einwaage
Edukt	Hydrochloric Acid	HCID 313	—
Edukt	Diisopropylethylamine	HCID 81531	—
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	2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethan-1-amine	HCID 28293775	—
Edukt	rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid	HCID 86640334	—
Lösungsmittel	Dichloromethane	HCID 6344	—
Lösungsmittel	Tetrahydrofuran	HCID 8028	—
Produkt	rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((R)-3,4-dihydroxy-butyl)-amide	HCID 86640349	54%

Reaktionsschritte

In a manner similar to the method described in Example 72a, rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid (0.2 g, 0.36 mmol) was reacted with 2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.15 g, 1.07 mmol), HATU (0.24 g, 0.64 mmol) and iPr2NEt (0.31 mL, 1.78 mmol) in CH2Cl2 at room temperature for 20 h, then reacted with aqueous HCl solution in tetrahydrofuran at room temperature for 2 h to give rac-(2R,3R,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((R)-3,4-dihydroxy-butyl)-amide as a white solid (0.1 g, 54%).

Herkunft & Nachweise

DOI	10.6084/m9.figshare.5104873.v1
Patentnummer	US08354444B2
Quelldatensatz	uspto-grants-2013_01
ORD ID	ord-3d6f6f53079d40b39a71f435e6f08e02
Quellennotiz	uspto-grants-2013_01