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

HRID 1963455Notes

Reaction equation

HRID 1963455 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 66732279(2S,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate

Product 1

HCID 469374815-((2S,4S)-2-(2,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 81.2%

Procedure

(2S,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (203 mg, 0.57 mmol) (from example 63, step 4) 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-((2S,4S)-2-(2,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (138 mg, 81%). 1H NMR (600 MHz, dmso) δ 1.62-1.70 (m, 1H), 1.80 (tt, 1H), 1.90-1.96 (m, 1H), 2.00-2.06 (m, 1H), 2.68 (dt, 1H), 2.85-2.91 (m, 1H), 3.20 (s, br., 1H), 3.90 (d, 1H), 5.86 (d, 1H), 7.43-7.56 (m, 2H). HRMS Calculated for [C14H13F3N2O2+H]+: 299.1007. Found: 299.1023

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-f1adbac5d3e44c7ba8916b9d2aeaa136
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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