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

Participants

Role	Name	HCID	Charge
Reactant	Diethyl Ether	HCID 3283	—
Reactant	5-Bromo-2-chloro-3-methylpyridine	HCID 285434	—
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-methylpyridin-3-yl)acetate	HCID 58447848	—

Reaction Conditions

Temperature	70 °C

Reaction Steps

To a sealed tube was added 5-bromo-2-chloro-3-methylpyridine 86-4 (4.69 g, 22.72 mmol), 0.5 M (2-tert-butoxy-2-oxoethyl) zinc(II) chloride in ether 86-5 (50 mL, 25 mmol), Pd(dba)2 (262 mg, 0.45 mmol), Q-phos (320 mg, 0.45 mmol), and THF (75 mL). The reaction mixture was bubbled with nitrogen for 1 minute and stirred at 70° C. for 4 hours. 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-methylpyridin-3-yl)acetate 86-6 as red oil. MS m/z 242.1 (M+1)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09238646B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-12d764d938844d6a9b8a65f121b1755f
Source note	uspto-grants-2016_01