Hydrogen Bromide → HCID 46938163, compound

HRID 1963364Notes

Reaction equation

HRID 1963364 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([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:7]=[CH:6][C:5]([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:4][CH:3]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68503481HCID 68503481, compound

Product 1

HCID 46938163HCID 46938163, compoundYield 23.8%

Procedure

(2R,4S)-Methyl 2-(4-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.86 g, 2.68 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 15.52 mL, 88.60 mmol) and the solution stirred at room temperature overnight. The solvent was evaporated and the residue was purified by preparative HPLC (Instrument: Agilent, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) and on a XBridge C18 column (10 μm 250×19 ID mm) using a gradient of 0-30% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 19 mL/min. 5-((2R,4S)-2-(4-Fluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (167 mg, 23%) was isolated. 1H NMR (400 MHz, dmso) δ 1.27-1.53 (m, 2H), 1.81-1.98 (m, 2H), 2.67-2.77 (m, 1H), 2.78-2.91 (m, 1H), 3.10 (d, 1H), 3.63 (d, 1H), 5.67-5.77 (m, 1H), 7.04-7.16 (m, 2H), 7.34-7.45 (m, 2H). HRMS Calculated for [C14H15FN2O2+H]+: 263.1196. Found: 263.1201

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by preparative HPLC (Instrument: Agilent, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) and on a XBridge C18 column (10 μm 250×19 ID mm)
  3. custombuffer over 20 minutes

Sources & evidence

ORD record
ord-d5c1e83d11b94a539e27525737e4ca8c
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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