1-Hydroxybenzotriazole → 3-(R)-Azido-2-(S)-[(4'-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	4-(4-Ethylphenyl)benzoic acid	HCID 521801	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(2S,3R)-2-amino-3-azido-butyric acid methylester hydrochloride	HCID 86643747	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	Ethyl acetate hexane	HCID 21226206	—
Product	3-(R)-Azido-2-(S)-[(4'-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester	HCID 59697227	67%

Reaction Steps

A EDC.HCl (249 mg, 1.3 mmol) was added to a stirred colorless solution of azido-Thr-OMe.HCl (4) (195 mg, 1.0 mmol), HOBT (158 mg, 1.0 mmol), 4′-Ethyl-biphenyl-4-carboxylic acid (5) (226 mg, 1.0 mmol) and DIEA (0.44 ml, 2.5 mmol) in DCM (10 ml) at rt under N2. After 24 h, the reaction had reached completion by TLC (Hexane/EtOAc (60:40) (Rf=0.3)) and LCMS. The reaction was evaporated under reduced pressure to a brown tar. The crude product was dissolved in EtOAc (100 ml) and washed with 0.2N aq. HCl (2×50 ml), aq. sat. NaHCO3 (50 ml), brine (50 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to yield a crude brown solid. The crude material was further purified by column chromatography eluting with Hexane/EtOAc (70:30) giving 245 mg (67% yield) of pure product after evaporation and drying in vacuo.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08153843B2
Source dataset	uspto-grants-2012_04
ORD ID	ord-b68d882f29bc40f8b2b820a8e180daf6
Source note	uspto-grants-2012_04