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

HRID 1963509Notes

Reaction equation

HRID 1963509 reaction equation
[CH:1]1([O:7][CH2:8][C@H:9]2[CH2:14][C@@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][N:10]2C(OC)=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br>>[CH:1]1([O:7][CH2:8][C@H:9]2[CH2:14][C@@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][NH:10]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68502091(2R,4S)-Methyl 2-(cyclohexyloxymethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667326875-((2R,4S)-2-(cyclohexyloxymethyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 3.2%

Procedure

(2R,4S)-Methyl 2-(cyclohexyloxymethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (190 mg, 0.56 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 4.43 mL, 25.27 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo 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-(cyclohexyloxymethyl)piperidin-4-yl)isoxazol-3(2H)-one (5 mg, 3%). 1H NMR (600 MHz, dmso) δ 1.03-1.25 (m, 6H), 1.32-1.48 (m, 2H), 1.55-1.68 (m, 2H), 1.70-1.90 (m, 4H), 2.56-2.66 (m, 1H), 2.68-2.79 (m, 2H), 2.99-3.06 (m, 1H), 3.06-3.83 (m, 3H), 5.70 (s, 1H). HRMS Calculated for [C15H24N2O3+H]+: 281.1865. Found: 281.1860

Workup

  1. customThe solvent was removed in vacuo
  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-d09b1a7917c547bd872307ff80d31b41
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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