Hydrogen Bromide → HCID 46937482, compound

HRID 1963458Notes

Reaction equation

HRID 1963458 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([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:4][C:3]=1[F:25].Br>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([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:4][C:3]=1[F:25]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68507161HCID 68507161, compound

Product 1

HCID 46937482HCID 46937482, compoundYield 83%

Procedure

(2R,4S)-Methyl 2-(4-chloro-3,5-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.39 g, 1.05 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 10 mL, 142.75 mmol) and stirred at room temperature for 18 h. 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,4S)-2-(4-chloro-3,5-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (272 mg, 83%). 1H NMR (600 MHz, dmso) δ 1.29 (q, 1H), 1.43 (dq, 1H), 1.82-1.89 (m, 1H), 1.97-2.04 (m, 1H), 2.70 (dt, 1H), 2.84 (tt, 1H), 3.06-3.12 (m, 1H), 3.68 (dd, 1H), 5.73 (s, 1H), 7.31 (d, 2H). HRMS Calculated for [C14H13ClF2N2O2+H]+: 315.0712. Found: 315.0707

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-34d2052cd4c349f582d1101ac9e9f53a
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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