Dimethyl Sulfide → Benzyl 2-(4-chlorophenyl)-6-ethyl-4-oxopiperidine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Dimethyl Sulfide	HCID 1068	—
Reactant	Boron trifluoride etherate	HCID 8000	—
Reactant	Ammonium Hydroxide	HCID 14923	—
Reactant	Ammonium Chloride	HCID 25517	—
Reactant	benzyl 2-ethyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate	HCID 53419195	—
Reactant	HCID 178478191	HCID 178478191	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	Benzyl 2-(4-chlorophenyl)-6-ethyl-4-oxopiperidine-1-carboxylate	HCID 59342384	33.3%

Reaction Conditions

Temperature	-78 °C

Reaction Steps

CuBr.SMe2 (5.6 g, 27.2 mmol) was added to dry THF (64 mL). It was cooled to −78° C. 4-Chlorophenylmagnesium bromide (27.2 mL, 1 M in THF, 27.2 mmol) was added to the mixture slowly over 1 hr at −78° C. Then BF3.Et2O (3.44 mL, 27.2 mmol) was added and the mixture was stirred for 5 min. Then ketone 82 (4 g, 8.1 mmol) in THF (55 mL) was added slowly over 1 hr at −78° C. After 2 hr stirring at −78° C., an aqueous solution of NH4Cl/conc. NH4OH (1:1, 20%, 60 mL) was added. The mixture was warmed to rt and extracted with EtOAc (200 mL×3), The combined organic layers were washed with brine, dried and concentrated to a residue and purified by silica gel chromatography (0-40% EtOAc/hexanes) to afford pure 83 (1 g, 2.7 mmol, 33%) as a mixture of cis stereoisomers.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07732609B2
Source dataset	uspto-grants-2010_06
ORD ID	ord-7b77112cbcbd41cea3bf4f3c5c428bda
Source note	uspto-grants-2010_06