Hydrogen Bromide → HCID 66732220, compound

HRID 1963419Notes

Reaction equation

HRID 1963419 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][N:10]1C(OC)=O.Br>>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][NH:10]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730406HCID 131730406, compound

Product 1

HCID 66732220HCID 66732220, compoundYield 86%

Procedure

Trans-methyl 2-(2-chloro-4-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (130 mg, 0.37 mmol) (from example 47, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 2.9 mL, 16.49 mmol) and stirred at room temperature for 16 h. The solvent was removed 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-(2-chloro-4-fluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (94 mg, 86%). 1H NMR (600 MHz, dmso) δ 1.50-1.60 (m, 1H), 1.79-1.88 (m, 1H), 1.95-2.01 (m, 1H), 2.06-2.12 (m, 1H), 2.70 (t, 1H), 2.88-2.96 (m, 1H), 3.20-3.24 (m, 1H), 4.01 (d, 1H), 5.95 (d, 1H), 7.21 (dt, 1H), 7.37 (dd, 1H), 7.68 (dd, 1H). HRMS Calculated for [C14H14ClFN2O2+H]+: 297.0806. Found: 297.0823

Workup

  1. customThe solvent was removed
  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-b12a0d9524f547339fe630e02c12e6a3
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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