Hydrogen Bromide → HCID 46937582, compound

HRID 1963484Notes

Reaction equation

HRID 1963484 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:12]2[CH2:17][C@@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][N:13]2C(OC)=O)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].Br>>[F:1][C:2]1[CH:3]=[C:4]([C@H:12]2[CH2:17][C@@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][NH:13]2)[CH:5]=[CH:6][C:7]=1[C:8]([F:9])([F:10])[F:11]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732416HCID 66732416, compound

Product 1

HCID 46937582HCID 46937582, compoundYield 55.4%

Procedure

(2R,4S)-Methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (319 mg, 0.82 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 6.5 mL, 36.97 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue was 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-(3-fluoro-4-(trifluoromethyl)phenyl)-piperidin-4-yl)isoxazol-3(2H)-one (150 mg, 55%). 1H NMR (600 MHz, dmso) δ 1.33 (q, 1H), 1.45 (dq, 1H), 1.84-1.90 (m, 1H), 1.99-2.05 (m, 1H), 2.72 (dt, 1H), 2.83-2.91 (m, 1H), 3.07-3.14 (m, 1H), 3.72-3.79 (m, 1H), 5.73 (s, 1H), 7.41 (d, 1H), 7.48 (d, 1H), 7.70 (t, 1H). HRMS Calculated for [C15H14F4N2O2+H]+: 331.1070. Found: 331.1058.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was 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-a150a3762c234abf87ef74714c37bbc9
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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