Hydrogen Bromide → HCID 66732396, compound

HRID 1963431Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([Cl: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]([Cl: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

Reactant 2

HCID 260Hydrogen Bromide

HCID 68500547HCID 68500547, compound

Product 1

HCID 66732396HCID 66732396, compoundYield 60.7%

Procedure

(2R,4R)-Methyl 2-(2,4-dichlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (75 mg, 0.20 mmol) (from example 51, step 3) was diluted with hydrogen bromide (33% in AcOH, 1062 μl, 6.06 mmol) and stirred at ambient temperature for 24 h. 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-(2,4-dichlorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (38 mg, 60%). 1H NMR (600 MHz, dmso) δ 1.47-1.54 (m, 1H), 1.78-1.85 (m, 1H), 1.93-1.99 (m, 1H), 2.05-2.11 (m, 1H), 2.67 (dt, 1H), 2.86-2.92 (m, 1H), 3.18-3.22 (m, 1H), 3.98 (dd, 1H), 5.93 (d, 1H), 7.41 (dd, 1H), 7.53 (d, 1H), 7.66 (d, 1H). HRMS Calculated for [C14H14Cl2N2O2+H]+: 313.0511. Found: 313.0494

Workup

customEvaporated
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-af61af096a1141a1b44008c22cd06334
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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