Ethyl 3-bromobenzoate → 3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)benzoic acid

https://huagongshe.com/reaction/2202026

Participants

Role	Name	HCID	Charge
Reactant	Ethyl 3-bromobenzoate	HCID 90488	—
Reactant	tert-Butyl piperazine-1-carboxylate	HCID 143452	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	Sodium t-butoxide	HCID 23676156	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)benzoic acid	HCID 44828726	42.2%

Reaction Conditions

Temperature	110 °C

Reaction Steps

The mixture of ethyl 3-bromobenzoate (500 mg, 2.33 mmol), tert-butyl piperazine-1-carboxylate (433 mg, 2.33 mmol) and NaOtBu (268 mg, 2.78 mmol), Pd2(dba)3 (20 mg, 0.034 mmol) and Xantphos (20 mg, 0,034 mmol) in anhydrous dioxane (10 mL) was heated to 110° C. for 10 h. The mixture was concentrated and the residue was partitioned in water, the solution was adjusted to pH=5, and extracted with DCM. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to afford the title compound that was used for next step (300 mg, Yield 42.2%). LCMS (m/z): 307.1 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09365519B2
Source dataset	uspto-grants-2016_06
ORD ID	ord-9fd552b8445747d0afc4372a39964a25
Source note	uspto-grants-2016_06