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

HRID 1963528Notes

Reaction equation

HRID 1963528 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2C(OC)=O)=[CH:4][CH:3]=1.Br>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][NH:9]2)=[CH:24][CH:25]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68502316(2S,4S)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469376455-((2S,4S)-2-(4-fluorophenethyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 63%

Procedure

(2S,4S)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (435 mg, 1.25 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 9.84 mL, 56.19 mmol) to give a yellow solution. The mixture was stirred at room temperature for 16 h, the solvent was removed 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-(4-fluorophenethyl)piperidin-4-yl)isoxazol-3(2H)-one (228 mg, 63%). 1H NMR (400 MHz, cd3od) δ 1.48 (dd, 1H), 1.64-1.97 (m, 3H), 2.13 (d, 1H), 2.30 (d, 1H), 2.66-2.80 (m, 2H), 2.84-3.10 (m, 3H), 3.34-3.43 (m, 1H), 5.51 (s, 1H), 6.97-7.05 (m, 2H), 7.19-7.28 (m, 2H). HRMS Calculated for [C16H19FN2O2+H]+: 291.1509. Found: 291.1497

Workup

  1. customto give a yellow solution
  2. customthe solvent was removed
  3. 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-33abdbca73054323b878bf5c6348c2da
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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