Isopropanol heptane → (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate

https://huagongshe.com/reaction/1963453

Participants

Role	Name	HCID	Charge
Reactant	Isopropanol heptane	HCID 21225753	—
Reactant	(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate	HCID 68503549	—
Reactant	trans-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate	HCID 131730420	—
Solvent	Acetonitrile	HCID 6342	—
Product	(2S,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate	HCID 66732279	20%
Product	(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate	HCID 68503549	25%

Reaction Steps

The mixture of cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)-piperidine-1-carboxylate and trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (1.027 g, 2.88 mmol) was subjected to chiral preparative HPLC (Column: CelluCoat (250×20), 5 μm particle size, mobile phase: Heptane/IPA 80/20, flow rate 18 mL/min) to yield (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (259 mg, 25%), Chiral purity A % 99.9, Optical rotation [α]D20=+50.3 (acetonitrile, c=1), and (2S,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (203 mg, 20%), Chiral purity A %: 99.9, Optical rotation [α]D20=+4.5 (acetonitrile, c=1)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08415378B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-f3922d264b2b4be8afd4e389601f9938
Source note	uspto-grants-2013_04