1,2-Dichloroethane → 2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonylamino-propionic acid methyl ester

Participants

Role	Name	HCID	Charge
Reactant	1,2-Dichloroethane	HCID 11	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methyl 3-((tert-butoxycarbonyl)amino)-L-alaninate	HCID 7021143	—
Reactant	((2r,3r)-3-Hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-n-(phenylmethoxy)carboxamide	HCID 59697601	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl acetate hexane	HCID 21226206	—
Product	2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonylamino-propionic acid methyl ester	HCID 57897028	91%

Reaction Steps

DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08101640B2
Source dataset	uspto-grants-2012_01
ORD ID	ord-22260034b5214ecb9440e68deadcbc83
Source note	uspto-grants-2012_01