Acetic Acid → 5-((2R,4R)-2-(4-fluorophenethyl)piperidin-4-yl)isoxazol-3(2H)-one

HRID 1963529Notes

Reaction equation

HRID 1963529 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C@@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2C(OC)=O)=[CH:4][CH:3]=1.C(O)(=O)C>Br>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C@@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][NH:9]2)=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 66732238(2R,4R)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469376465-((2R,4R)-2-(4-fluorophenethyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 65.6%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2R,4R)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (507 mg, 1.46 mmol) (from example 92, step 3) was dissolved in hydrogen bromide (33% in acetic acid (11.5 mL, 65.49 mmol) to give a yellow solution. The mixture was stirred at room temperature for 16 h, the solvent was removed 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,4R)-2-(4-fluorophenethyl)piperidin-4-yl)isoxazol-3(2H)-one (278 mg, 65%). 1H NMR (400 MHz, cd3od) δ 1.48 (q, 1H), 1.70 (dq, 1H), 1.78-1.96 (m, 2H), 2.09-2.17 (m, 1H), 2.26-2.34 (m, 1H), 2.66-2.80 (m, 2H), 2.86-3.09 (m, 3H), 3.35-3.43 (m, 1H), 5.52 (s, 1H), 6.98-7.05 (m, 2H), 7.21-7.26 (m, 2H). HRMS Calculated for [C16H19FN2O2+H]+: 291.1509. Found: 291.1483

Workup

  1. customto give a yellow solution
  2. customthe solvent was removed
  3. 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-973903c9268047a191c8e5d75aceca50
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…