Hydrogen Bromide → HCID 66732462, compound

HRID 1963580Notes

Reaction equation

HRID 1963580 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]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:28][C:25]([F:26])([F:27])[O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C@H:9]2[CH2:8][C@@H:7]([C:5]3[O:4][NH:3][C:2](=[O:1])[CH:6]=3)[CH2:12][CH2:11][NH:10]2)=[CH:19][CH:20]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732768HCID 66732768, compound

Product 1

HCID 66732462HCID 66732462, compoundYield 9.4%

Procedure

(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethoxy)benzyl)-piperidine-1-carboxylate (0.690 g, 1.72 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 13.58 mL, 77.56 mmol) and the mixture stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx III, 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-(4-(trifluoromethoxy)benzyl)-piperidin-4-yl)isoxazol-3(2H)-one (55 mg, 9.4%). 1H NMR (600 MHz, dmso) δ 1.07 (q, 1H), 1.34 (dq, 1H), 1.69-1.78 (m, 2H), 2.45-2.74 (m, 5H), 2.93-2.99 (m, 1H), 5.64 (s, 1H), 7.20-7.25 (m, 2H), 7.26-7.32 (m, 2H). HRMS Calculated for [C16H17F3N2O3+H]+: 343.1270. Found: 343.1241

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by preparative HPLC (Instrument: FractionLynx III, 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-388a9878a5aa4c1ba5da1166a7202ab8
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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