Hydrogen Bromide → HCID 66732314, compound

HRID 1963650Notes

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]([CH2:17][C:18]3[CH:23]=[C:22]([F:24])[C:21]([F:25])=[C:20]([F:26])[CH:19]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:26][C:20]1[CH:19]=[C:18]([CH:23]=[C:22]([F:24])[C:21]=1[F:25])[CH2:17][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

Reactant 2

HCID 260Hydrogen Bromide

HCID 68504120HCID 68504120, compound

Product 1

HCID 66732314HCID 66732314, compoundYield 71%

Procedure

(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorobenzyl)piperidine-1-carboxylate (598 mg, 1.61 mmol) (from example 143, step 3) was dissolved in hydrogen bromide (33% in AcOH, 7 mL, 99.92 mmol) and stirred at room temperature for 20 h. The solvent was evaporated in vacuo 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,4R)-2-(3,4,5-trifluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (357 mg, 70.8%). 1H NMR (600 MHz, dmso) δ 1.05 (q, 1H), 1.32 (dq, 1H), 1.70-1.78 (m, 2H), 2.33-3.58 (m, 6H), 5.68 (s, 1H), 7.12-7.19 (m, 2H). HRMS Calculated for [C15H15F3N2O2+H]+: 313.1164. Found: 313.1158

Workup

customThe solvent was evaporated in vacuo
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-ad4d5b4ab2db41eeb65aa74779d9d83b
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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