Hydrochloric Acid → Diethyl 2-(difluoromethyl)-4-ethyl-6-(trifluoromethyl)-3,5-pyridinedicarboxylate

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	1,4-Dihydro-2,6-bis(trifluoromethyl)-4-ethylpyridine-3,5-dicarboxylic acid diethyl ester	HCID 13957621	—
Reactant	1,2,3,4,6,7,8,10A-octahydropyrimido[1,2-a]azepine	HCID 15072656	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	Diethyl 2-(difluoromethyl)-4-ethyl-6-(trifluoromethyl)-3,5-pyridinedicarboxylate	HCID 13957657	78.5%

Reaction Steps

A mixture of 1558 g (4.00 moles) of diethyl 2,6-bis(trifluoromethyl)-1,4-dihydro-4-ethyl-3,5-pyridinedicarboxylate, 628 g (4.0 moles) of 1,8-diazabicyclo-[5.4.0]-undec-5-ene (DBU), and 500 ml of tetrahydrofuran is held at reflux for 19 hours, cooled and poured into a mixture of 2 kg of ice and 250 ml of concentrated hydrochloric acid. The organic layer is separated and the aqueous layer extracted with 500 ml of CH2Cl2 twice. The combined organic materials are dried (MgSO4) and concentrated. The residue is kugelrohr distilled at 1 torr (pot temperature of 150°-160° C.) to give 1158 g (78.5%) of desired product, nD25 1.4458.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US05142055
Source dataset	uspto-grants-1992_08
ORD ID	ord-10f23d9c4c964db0a53c596e81f1cf66
Source note	uspto-grants-1992_08