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

HRID 1963568Notes

Reaction equation

HRID 1963568 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]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:26][C:24]([F:25])([F:27])[C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=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 66732075(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate

Product 1

HCID 469377635-((2S,4R)-2-(3-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 68%

Procedure

(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate (0.64 g, 1.67 mmol) (from example 107, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 5 mL, 71.37 mmol) and stirred at room temperature for 41 h. Reaction mixture was evaporated and restarted under the same conditions. After 28 h solvents evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx I, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-((2S,4R)-2-(3-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (368 mg, 68%). 1H NMR (600 MHz, DMSO) δ 1.07-1.15 (m, 1H), 1.36 (dq, 1H), 1.74-1.80 (m, 2H), 2.54-2.58 (m, 1H), 2.64-2.79 (m, 4H), 2.96-3.01 (m, 1H), 5.66 (s, 1H), 7.50-7.59 (m, 4H). HRMS Calculated for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1333

Workup

  1. customReaction mixture
  2. customwas evaporated
  3. customAfter 28 h solvents evaporated
  4. customthe residue purified by preparative HPLC (Instrument: FractionLynx I, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)

Sources & evidence

ORD record
ord-51a3dd5b0c3c4206a4119950d64197a8
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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