Sodium Bicarbonate → [4'-[3-Methyl-4-[[[((R)-1-phenylethyl)oxy]carbonyl]amino]isoxazol-5-yl]biphenyl-4-yl]acetic acid ethyl ester

Participants

Role	Name	HCID	Charge
Reactant	Sodium Bicarbonate	HCID 516892	—
Reactant	Ethyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate	HCID 46737998	—
Reactant	(1R)-1-Phenylethyl N-(5-(4-bromophenyl)-3-methyl-4-isoxazolyl)carbamate	HCID 66660383	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Product	[4'-[3-Methyl-4-[[[((R)-1-phenylethyl)oxy]carbonyl]amino]isoxazol-5-yl]biphenyl-4-yl]acetic acid ethyl ester	HCID 67352169	—

Reaction Conditions

Temperature	90 °C

Reaction Steps

[5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester (39 g, 97.2 mmol), [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (31 g, 107 mmol), and sodium bicarbonate (32.6 g, 389 mmol) were combined in 3:1 DME:H2O (500 mL), and the mixture was purged with N2 for 15 minutes. (1,1′-Bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (2.13 g, 2.91 mmol) was added, and the reaction was purged with N2 for an additional 10 minutes and then stirred at 90° C. overnight. The mixture was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with H2O, dried over MgSO4, filtered, and concentrated, and the residue was purified by silica gel chromatography (EtOAc/hexane gradient) to give the title compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08048902B2
Source dataset	uspto-grants-2011_11
ORD ID	ord-ef9395f576574672bca26cf195d16bd4
Source note	uspto-grants-2011_11