Acetic Acid → HCID 46937477, compound

HRID 1963447Notes

Reaction equation

HRID 1963447 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.C(O)(=O)C>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

4

Reactant 2

HCID 176Acetic AcidHCID 66732940HCID 66732940, compound

Product 1

HCID 46937477HCID 46937477, compoundYield 67.8%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (164 mg, 0.46 mmol) was dissolved in hydrogen bromide (33% in acetic acid (3.63 mL, 20.71 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-(3,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (93 mg, 67%). 1H NMR (600 MHz, dmso) δ 1.29 (q, 1H), 1.43 (dq, 1H), 1.82-1.89 (m, 1H), 1.96-2.02 (m, 1H), 2.70 (dt, 1H), 2.79-2.87 (m, 1H), 3.05-3.12 (m, 1H), 3.64 (dd, 1H), 5.72 (s, 1H), 7.26-7.34 (m, 2H). HRMS Calculated for [C14H13F3N2O2+H]+: 299.1007. Found: 299.1002

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-4b938db048ff4264998543c252029f07
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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