Hydrogen Bromide → HCID 46937478, compound

HRID 1963448Notes

Reaction equation

HRID 1963448 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([C@@H:7]2[CH2:12][CH2:11][N:10](C(OC)=O)[C@H:9]([C:17]3[CH:22]=[C:21]([F:23])[C:20]([F:24])=[C:19]([F:25])[CH:18]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:25][C:19]1[CH:18]=[C:17]([C@@H:9]2[CH2:8][C@H:7]([C:5]3[O:4][NH:3][C:2](=[O:1])[CH:6]=3)[CH2:12][CH2:11][NH:10]2)[CH:22]=[C:21]([F:23])[C:20]=1[F:24]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 68502355HCID 68502355, compound

Product 1

HCID 46937478HCID 46937478, compoundYield 63.3%

Procedure

(2S,4R)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (160 mg, 0.45 mmol) (from example 60, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 3.54 mL, 20.21 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-((2S,4R)-2-(3,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (85 mg, 63%) 1H NMR (600 MHz, dmso) δ 1.29 (q, 1H), 1.43 (qd, 1H), 1.83-1.88 (m, 1H), 1.97-2.02 (m, 1H), 2.70 (td, 1H), 2.80-2.87 (m, 1H), 3.06-3.12 (m, 1H), 3.64 (dd, 1H), 5.73 (s, 1H), 7.27-7.34 (m, 2H). HRMS Calculated for [C14H13F3N2O2+H]+: 299.1007. Found: 299.1037

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-7a80f9cb4f614266bcfaf4311511f320
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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