Hydrogen Bromide → HCID 66732779, compound

HRID 1963624Notes

Reaction equation

HRID 1963624 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([F:25])[CH:24]=1)[CH2:5][C@H:6]1[CH2:11][C@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][N:7]1C(OC)=O.Br>>[F:25][C:23]1[CH:22]=[C:4]([CH:3]=[C:2]([F:1])[CH:24]=1)[CH2:5][C@H:6]1[CH2:11][C@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][NH:7]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68502775HCID 68502775, compound

Product 1

HCID 66732779HCID 66732779, compoundYield 25.1%

Procedure

(2R,4R)-Methyl 2-(3,5-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.244 g, 0.69 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 5.46 mL, 31.16 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated 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-((2R,4R)-2-(3,5-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (51 mg, 25%). 1H NMR (600 MHz, dmso) δ 1.44-1.51 (m, 1H), 1.65-1.80 (m, 3H), 2.52-2.60 (m, 1H), 2.65-2.70 (m, 2H), 2.76-2.83 (m, 1H), 2.86-2.94 (m, 1H), 3.09-3.14 (m, 1H), 5.74 (s, 1H), 6.90-6.95 (m, 2H), 7.00 (tt, 1H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1276

Workup

  1. customThe solvent was evaporated
  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-5269feac722c45bb8a18b078ab746e15
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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