Acetic Acid → 5-(trans-2-(Cyclohexyloxymethyl)piperidin-4-yl)isoxazol-3(2h)-one

HRID 1963512Notes

Reaction equation

HRID 1963512 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.C(O)(=O)C>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

4

Reactant 2

HCID 176Acetic AcidHCID 131730444trans-Methyl 2-(cyclohexyloxymethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667318395-(trans-2-(Cyclohexyloxymethyl)piperidin-4-yl)isoxazol-3(2h)-oneYield 15%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

Trans-methyl 2-(cyclohexyloxymethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (121 mg, 0.36 mmol) was dissolved in hydrogen bromide (33% in acetic acid, (2.75 mL, 15.69 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-(trans-2-(cyclohexyloxymethyl)piperidin-4-yl)isoxazol-3(2H)-one (15 mg, 15%). 1H NMR (600 MHz, dmso) δ 1.09-1.25 (m, 5H), 1.38-1.53 (m, 2H), 1.55-1.65 (m, 2H), 1.65-1.83 (m, 5H), 2.55-2.63 (m, 1H), 2.69-2.80 (m, 2H), 3.02-3.88 (m, 4H), 5.76 (s, 1H). HRMS Calculated for [C15H24N2O3+H]+: 281.1865. Found: 281.1879

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-ba8dea89e0c04b7dbb495fcad678fc19
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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