Acetic Acid → HCID 46937583, compound

HRID 1963485Notes

Reaction equation

HRID 1963485 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].C(O)(=O)C>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

4

Reactant 2

HCID 176Acetic AcidHCID 66732540HCID 66732540, compound

Product 1

HCID 46937583HCID 46937583, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2S,4R)-Methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (332 mg, 0.85 mmol) was dissolved in hydrogen bromide (33% in acetic acid (6.74 mL, 38.47 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-((2S,4R)-2-(3-fluoro-4-(trifluoromethyl)phenyl)-piperidin-4-yl)isoxazol-3(2H)-one (174 mg, 62%). 1H NMR (600 MHz, dmso) δ 1.32 (q, 1H), 1.45 (dq, 1H), 1.85-1.90 (m, 1H), 2.00-2.04 (m, 1H), 2.72 (dt, 1H), 2.87 (tt, 1H), 3.08-3.13 (m, 1H), 3.73-3.77 (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: 331.1067.

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-d88077ae138c49fca54075d149f2b6e3
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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