Potassium Phosphate, Tribasic → US10023592, Example 291

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	5-Bromo-3-(difluoromethoxy)-1-methylpyridin-2-one	HCID 118022074	—
Reactant	2-[2-(2,4-Difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane	HCID 123957397	—
Catalyst	Water	HCID 962	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	US10023592, Example 291	HCID 118022412	24%

Reaction Conditions

Temperature	70 °C

Reaction Steps

A mixture of 5-bromo-3-(difluoromethoxy)-1-methylpyridin-2-one (50 mg, 0.20 mmol), 2-[2-(2,4-difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (79 mg, 0.18 mmol), Pd(dppf)Cl2 (11 mg) and K3PO4 (76 mg, 0.36 mmol) in dioxane (5 mL) and water (5 drops) was purged with nitrogen, capped, and heated to 70° C. for 8 h. After the mixture was filtered, the filtrate was concentrated in vacuo and purified by prep-HPLC to afford the title compound (21 mg, 22%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.62 (d, J=2.0 Hz, 1H) 7.54 (d, J=2.0 Hz, 1H) 7.40 (d, J=2.0 Hz, 1H) 7.29 (d, J=2.0 Hz, 1H) 7.09-6.96 (m, 3H) 6.93-6.88 (m, 1H) 6.78 (m, 1H) 4.21 (s, 2H) 3.70 (s, 3H) 2.97 (q, J=7.6 Hz, 2H) 1.43 (t, J=7.6 Hz, 3H). LCMS (M+H)+=486.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09034900B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-f21f48878bd441a9a7456001acf84611
Source note	uspto-grants-2015_05