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

HRID 1963454Notes

Reaction equation

HRID 1963454 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([C@H:7]2[CH2:12][CH2:11][N:10](C(OC)=O)[C@@H:9]([C:17]3[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=3[F:25])[CH2:8]2)[O:4][NH:3]1.Br>>[F:25][C:18]1[CH:19]=[C:20]([F:24])[C:21]([F:23])=[CH:22][C:17]=1[C@H:9]1[CH2:8][C@@H:7]([C:5]2[O:4][NH:3][C:2](=[O:1])[CH:6]=2)[CH2:12][CH2:11][NH:10]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68503549(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate

Product 1

HCID 469374805-((2R,4S)-2-(2,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 74%

Procedure

(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (259 mg, 0.73 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 4 mL, 22.84 mmol) and the mixture 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-(2,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (161 mg, 74%). 1H NMR (600 MHz, dmso) δ 1.36 (q, 1H), 1.45 (dq, 1H), 1.83-1.90 (m, 1H), 1.91-1.97 (m, 1H), 2.74 (dt, 1H), 2.90 (tt, 1H), 3.06-3.13 (m, 1H), 3.91 (d, 1H), 5.74 (d, 1H), 7.44-7.57 (m, 2H). HRMS Calculated for [C14H13F3N2O2+H]+: 299.1007. Found: 299.1021

Workup

  1. customThe solvent was evaporated
  2. 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-f4d5df5b0ef047228e5b0d8da9429f75
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…