Ethyl Acetate → (1s,2r)-4'-(2-Benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid

Participants

Role	Name	HCID	Charge
Reactant	Ethyl Acetate	HCID 8857	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate	HCID 151348	—
Reactant	methyl(2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoate	HCID 59697585	—
Reactant	((2r,3r)-3-Hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-n-(phenylmethoxy)carboxamide	HCID 59697601	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(1s,2r)-4'-(2-Benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid	HCID 87102973	13%

Reaction Steps

To a suspension of 4,4′-biphenyldicarboxylic acid 2 (1.360 g, 5.61 mmol) in DMF (180 mL) was added BOP (2.007 g, 4.54 mmol) and DIEA (1.7 mL, 9.8 mmol). A solution of (1S,2R)-2-amino-3,N-bis-benzyloxy-butyramide 1 (944 mg, 3.00 mmol) in DMF (20 mL) was added and the reaction stirred for 18 h. The solution was diluted with EtOAc (250 mL) and washed with 1.0 M HCl (500 mL). The aqueous layer was extracted with EtOAc (250 mL) and the organic layers combined. The organic layer was washed with 1.0 M HCl (250 mL), dried over MgSO4, and concentrated to give a crude yellow solid. Purification by silica gel chromatography (60:1 CH2Cl2/MeOH) gave 210 mg (1S,2R)-4′-(2-benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid 3. (13% yield) as a yellow solid. Rf=0.80 (10:1 CH2Cl2/MeOH); LRMS (ES+) m/z 539.1 (C32H30N2O6+H requires 539.22).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08153843B2
Source dataset	uspto-grants-2012_04
ORD ID	ord-a76cc6dac08c4b7cad3daf2beff2cae6
Source note	uspto-grants-2012_04