Hydrogen Bromide → HCID 66732362, compound

HRID 1963424Notes

Reaction equation

HRID 1963424 reaction equation
[Cl: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][C:3]=1[F:24].Br>>[Cl: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][C:3]=1[F:24]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730409HCID 131730409, compound

Product 1

HCID 66732362HCID 66732362, compoundYield 56%

Procedure

Trans-methyl 2-(4-chloro-3-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (49 mg, 0.14 mmol) was dissolved in hydrogen bromide (33% in AcOH, 2 mL, 11.42 mmol) and stirred at room temperature for 5 h. The reaction was heated to 50° C. for 3 h. The reaction mixture was evaporated 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-(4-chloro-3-fluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (23 mg, 56%). 1H NMR (600 MHz, dmso) δ 1.72-1.81 (m, 2H), 1.82-1.89 (m, 1H), 1.97-2.04 (m, 1H), 2.64-2.71 (m, 1H), 2.77-2.83 (m, 1H), 3.06-3.12 (m, 1H), 3.72 (dd, 1H), 5.96 (s, 1H), 7.23 (dd, 1H), 7.40 (dd, 1H), 7.49 (t, 1H). HRMS Calculated for [C14H14ClFN2O2+H]+: 297.0806. Found: 297.0807

Workup

  1. temperatureThe reaction was heated to 50° C. for 3 h
  2. customThe reaction mixture was evaporated in vacuo
  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-28b75179331e4b3889b043947ca321b4
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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