Acetic Acid → HCID 46938270, compound

HRID 1963418Notes

Reaction equation

HRID 1963418 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][N:10]1C(OC)=O.C(O)(=O)C>Br>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][NH:10]1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 66739064HCID 66739064, compound

Product 1

HCID 46938270HCID 46938270, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2R,4S)-methyl 2-(2-chloro-4-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (382 mg, 1.08 mmol) was dissolved in hydrogen bromide (33% in acetic acid (8.5 mL, 48.46 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo 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-(2-chloro-4-fluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (304 mg, 95%). 1H NMR (600 MHz, dmso) δ 1.24 (q, 1H), 1.47 (dq, 1H), 1.85-1.91 (m, 1H), 1.97-2.02 (m, 1H), 2.75 (dt, 1H), 2.87 (tt, 1H), 3.09-3.14 (m, 1H), 3.97 (d, 1H), 5.73 (d, 1H), 7.19 (dt, 1H), 7.37 (dd, 1H), 7.66 (dd, 1H). HRMS Calculated for [C14H14ClFN2O2+H]+: 297.0806. Found: 297.0834

Workup

  1. customThe solvent was removed in vacuo
  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-fd195543a3b746e9a348959af5ff7a10
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…