Sodium Carbonate → {3-[2-Chloro-5-(3,6-dihydro-2H-pyran-4-YL)-pyrimidin-4-yloxy]-cyclobutyl}-carbamic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	3,6-Dihydro-2H-pyran-4-boronic acid pinacol ester	HCID 11218053	—
Reactant	[3-(5-Bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester	HCID 58548640	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	{3-[2-Chloro-5-(3,6-dihydro-2H-pyran-4-YL)-pyrimidin-4-yloxy]-cyclobutyl}-carbamic acid tert-butyl ester	HCID 58548678	43.3%

Reaction Steps

To a solution of [3-(5-bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester (5.1 g, 13.3 mmol) in dioxane (80 mL) was treated with Na2CO3 (2.8 g, 26.6 mmol) in 15 mL of H2O as a solution, followed by additional of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (3.3 g 16.0 mmol) and Pd(dppf)Cl2 (974 mg, 1.33 mmol). The resulting mixture was heated at refluxing overnight under N2 atmosphere. TLC showed that most of the staring materials were consumed completely. The solution was filtered, and the filter was concentrated. And the residue was purified by silica gel chromatography to give the product (2.2 g, 5.76 mmol, 43%). ESI-MS (M+1): 382 calc. for C18H24ClN3O4 381.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08952037B2
Source dataset	uspto-grants-2015_02
ORD ID	ord-95ec245050c34860982a5e95d9e58115
Source note	uspto-grants-2015_02