Hydrogen Bromide → 5-((2R,4S)-2-(2,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one

HRID 1963410Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][N:10]1C(OC)=O.Br>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][NH:10]1

Participants

Reactant 2

HCID 260Hydrogen Bromide

HCID 68503711HCID 68503711, compound

Product 1

HCID 469383185-((2R,4S)-2-(2,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 60.3%

Procedure

(2R,4S)-methyl 2-(2,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (187 mg, 0.55 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 4.36 mL, 24.87 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-((2R,4S)-2-(2,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (93 mg, 60%). 1H NMR (600 MHz, dmso) δ 1.36 (q, 1H), 1.46 (dq, 1H), 1.83-1.89 (m, 1H), 1.90-1.95 (m, 1H), 2.72 (dt, 1H), 2.89 (tt, 1H), 3.06-3.12 (m, 1H), 3.89 (dd, 1H), 5.73 (s, 1H), 7.03 (dt, 1H), 7.11-7.17 (m, 1H), 7.52-7.59 (m, 1H). HRMS Calculated for [C14H14F2N2O2+H]+: 281.1101. Found: 281.1106

Workup

customThe solvent was evaporated
customthe residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)

Sources & evidence

ORD record: ord-cbaf3a578502478c9acae2d1e40b43fc
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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