Hydrogen Bromide → HCID 66732609, compound

HRID 1963614Notes

Reaction equation

HRID 1963614 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[CH2:4][C@@H:5]1[CH2:10][C@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][N:6]1C(OC)=O.Br>>[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[CH2:4][C@@H:5]1[CH2:10][C@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][NH:6]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732492HCID 66732492, compound

Product 1

HCID 66732609HCID 66732609, compoundYield 77%

Procedure

(2S,4R)-Methyl 2-(2,6-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (344 mg, 0.98 mmol) (from example 127, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 8 mL, 45.68 mmol) and the mixture stirred at room temperature for 24 h. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx III, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-((2S,4R)-2-(2,6-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (222 mg, 77%). 1H NMR (600 MHz, cd3od) δ 1.47 (q, 1H), 1.68 (dq, 1H), 1.96-2.07 (m, 2H), 2.79-3.02 (m, 4H), 3.18-3.25 (m, 1H), 3.27-3.34 (m, 1H), 5.49 (s, 1H), 6.95-7.01 (m, 2H), 7.28-7.36 (m, 1H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1240

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by preparative HPLC (Instrument: FractionLynx III, 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-c68abd743a87453186789a9349a98ea0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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