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	70 °C

Reaction Steps

In a sealed tube, a mixture of 5-bromo-2-chloro-3-fluoropyridine 205-1 (631 mg, 3 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride 205-2 in ether (6.6 mL, 3.3 mmol), Pd(dba)2 (87 mg, 0.15 mmol), 1,2,3,4,5-pentaphenyl-1′-(di-t-butylphosphino)ferrocene (Q-phos, 107 mg, 0.15 mmol), and THF (12 mL) under argon was stirred at 70° C. for 18 hours. After cooled to room temperature, 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, eluted with 30% ethyl acetate in hexane to give tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate 205-3 as a brown oil. 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-e7816d1529d0422babaa825b34cb5707
Source note	uspto-grants-2013_10