Diethyl Ether → Tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate

Participants

Role	Name	HCID	Charge
Reactant	Diethyl Ether	HCID 3283	—
Reactant	5-Bromo-2-chloro-3-fluoropyridine	HCID 2763285	—
Reactant	HCID 178451183	HCID 178451183	—
Catalyst	(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium	HCID 6505921	—
Catalyst	Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene	HCID 129828017	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	Tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate	HCID 58365072	—

Reaction Conditions

Temperature	100 °C

Reaction Steps

To a sealed tube were added 5-bromo-2-chloro-3-fluoropyridine 190-1 (210 mg, 1.0 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride 86-5 in ether (2.4 mL, 1.2 mmol), Pd(dba)2 (29 mg, 0.005 mmol), Q-phos (71 mg, 0.10 mmol) and THF (3 mL). The reaction mixture was bubbled with nitrogen for 1 minute and stirred at 100° C. for 1 hour. After cooling to room temperature, all the solvents were evaporated and the residue was redissolved in ethyl acetate, washed with water and brine, dried over Na2SO4 and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography and eluted with 20% ethyl acetate in hexane to give tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate 190-3. MS m/z 246.1 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08546396B2
Source dataset	uspto-grants-2013_10
ORD ID	ord-4ca27f869f214fa4b13a34e617d160b5
Source note	uspto-grants-2013_10