Triethylamine → (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester

Participants

Role	Name	HCID	Charge
Reactant	Triethylamine	HCID 8471	—
Reactant	2-Thiopheneacetic acid	HCID 15970	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride	HCID 25017086	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester	HCID 67506137	—

Reaction Steps

To a solution of thiophen-2-yl-acetic acid (0.144 mmol) in DMF (5 mL) is added HATU (0.216 mmol). After stirring the mixture at room temperature for 10 minutes, (2R,4S)-4-amino-5-biphenyl-4-yl-2-methyl-pentanoic acid ethyl ester hydrochloride (0.144 mmol) and triethylamine (0.359 mmol) is added and the mixture is stirred at room temperature for 18 hours. The mixture is poured into ethyl acetate and the mixture is washed with aqueous 1M HCl and brine. The organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure to give (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester which is used directly in the subsequent hydrolysis reaction.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08263629B2
Source dataset	uspto-grants-2012_09
ORD ID	ord-d6cd1163e8ac4da492eda3ddea1c402f
Source note	uspto-grants-2012_09