Sodium Bicarbonate → tert-butyl (5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methylcarbamate

Participants

Role	Name	HCID	Charge
Reactant	Sodium Bicarbonate	HCID 516892	—
Reactant	tert-Butyl ((5-bromopyridin-2-yl)methyl)carbamate	HCID 45789881	—
Reactant	2,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanone	HCID 86695414	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	Toluene ethanol	HCID 21863594	—
Product	tert-butyl (5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methylcarbamate	HCID 86695413	77%

Reaction Conditions

Temperature	80 °C

Reaction Steps

To a solution of the product of Step 3, Example 22 (1000 mg, 2.4 mmol) in toluene/ethanol (30:20 mL) is added commercially available tert-butyl (5-bromopyridin-2-yl)methylcarbamate (695 mg, 2.42 mmol), sodium bicarbonate (5 mL of a saturated solution) and Pd(dppf)2Cl2 (90 mg, 0.12 mmol). The reaction mixture is heated to 80° C. while stirring under nitrogen for 4 hours. The reaction mixture is cooled and diluted with water. Contents are extracted with ethylacetate (2×75 mL) and the combined organic phase is dried (Na2SO4) and concentrated under vacuum. Crude material is chromatographed (80 g Redi-Sep column) eluting from 100% hexanes to 90:10 ethylacetate:hexanes to afford the title compound (912 mg): m/z (Cl) M+H 494.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09340564B2
Source dataset	uspto-grants-2016_05
ORD ID	ord-a25438ba19c54852b978835b938f1665
Source note	uspto-grants-2016_05