Hydrogen Bromide → HCID 46938323, compound

HRID 1963436Notes

Reaction equation

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

Participants

Reactant 2

HCID 260Hydrogen Bromide

HCID 66734693HCID 66734693, compound

Product 1

HCID 46938323HCID 46938323, compoundYield 60.4%

Procedure

(2S,4R)-Methyl 2-(3,5-dichlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1 g, 2.69 mmol) (from example 55, step 3) was dissolved in hydrogen bromide (33% in AcOH, 4.67 mL, 80.82 mmol) and stirred overnight. 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-((2S,4R)-2-(3,5-dichlorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (509 mg, 60%). 1H NMR (600 MHz, dmso) δ 1.32 (q, 1H), 1.44 (dq, 1H), 1.84-1.89 (m, 1H), 1.97-2.02 (m, 1H), 2.70 (dt, 1H), 2.84 (tt, 1H), 3.07-3.12 (m, 1H), 3.67 (dd, 1H), 5.75 (s, 1H), 7.42 (d, 2H), 7.44 (t, 1H). HRMS Calculated for [C14H14Cl2N2O2+H]+: 313.0511. Found: 313.0516

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-6410327d224b43c3a352b405be58feb0
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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