Hydrogen Bromide → HCID 66732268, compound

HRID 1963574Notes

Reaction equation

HRID 1963574 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][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])[CH2:8]2)[O:4][NH:3]1.Br>>[F:27][C:24]([F:25])([F:26])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[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

3

Reactant 2

HCID 260Hydrogen BromideHCID 68504952(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate

Product 1

HCID 66732268HCID 66732268, compoundYield 71%

Procedure

(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate (597 mg, 1.55 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 10 mL, 57.10 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-(2-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (358 mg, 71%). 1H NMR (600 MHz, cd3od) δ 1.68 (q, 1H), 1.84 (qd, 1H), 2.11 (d, 1H), 2.22 (d, 1H), 3.02-3.20 (m, 3H), 3.21-3.32 (m, 1H), 3.51 (d, 1H), 3.57-3.67 (m, 1H), 5.74 (s, 1H), 7.44-7.56 (m, 2H), 7.64 (t, 1H), 7.74 (d, 1H). HRMS Calculated for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1328

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-e39ce872d1944a358357b0294cd4d75c
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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