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

HRID 1963390Notes

Reaction equation

HRID 1963390 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([C@H:11]2[CH2:16][C@@H:15]([C:17]3[O:21][NH:20][C:19](=[O:22])[CH:18]=3)[CH2:14][CH2:13][N:12]2C(OC)=O)[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Br>>[C:1]([C:5]1[CH:6]=[C:7]([C@H:11]2[CH2:16][C@@H:15]([C:17]3[O:21][NH:20][C:19](=[O:22])[CH:18]=3)[CH2:14][CH2:13][NH:12]2)[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68501687(2R,4S)-Methyl 2-(3-tert-butylphenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469382645-((2R,4S)-2-(3-tert-butylphenyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 37.5%

Procedure

(2R,4S)-Methyl 2-(3-tert-butylphenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.340 g, 0.95 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 5.49 mL, 31.35 mmol) and the solution stirred at room temperature overnight. The solvent was evaporated 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-((2R,4S)-2-(3-tert-butylphenyl)piperidin-4-yl)isoxazol-3(2H)-one (107 mg, 37%). 1H NMR (400 MHz, dmso) δ 1.26 (s, 9H), 1.32-1.43 (m, 1H), 1.43-1.54 (m, 1H), 1.81-1.90 (m, 1H), 1.90-1.99 (m, 1H), 2.68-2.78 (m, 1H), 2.80-2.91 (m, 1H), 3.08-3.16 (m, 1H), 3.59-3.66 (m, 1H), 5.72 (s, 1H), 7.13-7.29 (m, 3H), 7.37 (s, 1H). HRMS Calcd for [C18H24N2O2+H]+: 301.1916. Found: 301.1909.

Workup

  1. customThe solvent was evaporated
  2. 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-5c14fb2337cc48bb89b3d29be6c081c3
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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