Hydrogen Bromide → HCID 46938268, compound

HRID 1963401Notes

Reaction equation

HRID 1963401 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:18]=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:26][C:23]([F:24])([F:25])[C:20]1[N:19]=[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][CH:21]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66740525HCID 66740525, compound

Product 1

HCID 46938268HCID 46938268, compoundYield 68.6%

Procedure

(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)-piperidine-1-carboxylate (74.5 mg, 0.20 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 1.58 mL, 9.03 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,4S)-2-(6-(trifluoromethyl)pyridin-3-yl)piperidin-4-yl)isoxazol-3(2H)-one (43 mg, 68%), 1H NMR (600 MHz, dmso) δ 1.36-1.53 (m, 2H), 1.89 (d, 1H), 2.04 (d, 1H), 2.70-2.78 (m, 1H), 2.90 (tt, 1H), 3.09-3.16 (m, 1H), 3.83 (d, 1H), 5.75 (s, 1H), 7.84 (d, 1H), 8.04 (dd, 1H), 8.75 (d, 1H). HRMS Calculated for [C14H14F3N3O2+H]+: 314.1116. Found: 314.1134

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-dd1a314e770545ac9789e4c106ac3529
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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