Hydrogen Bromide → HCID 66732652, compound

HRID 1963524Notes

Reaction equation

HRID 1963524 reaction equation
[F:1][C:2]1([F:25])[CH2:7][CH2:6][CH:5]([CH2:8][C@H:9]2[CH2:14][C@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][N:10]2C(OC)=O)[CH2:4][CH2:3]1.Br>>[F:25][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([CH2:8][C@H:9]2[CH2:14][C@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][NH:10]2)[CH2:4][CH2:3]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730450HCID 131730450, compound

Product 1

HCID 66732652HCID 66732652, compoundYield 28%

Procedure

Trans-methyl 2-((4,4-difluorocyclohexyl)methyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (0.267 g, 0.75 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 5.87 mL, 33.53 mmol) and the mixture 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-(trans-2-((4,4-difluorocyclohexyl)methyl)-piperidin-4-yl)isoxazol-3(2H)-one (63 mg, 28%). 1H NMR (600 MHz, dmso) δ 0.99-1.19 (m, 3H), 1.27-1.35 (m, 1H), 1.38-1.46 (m, 1H), 1.46-1.55 (m, 1H), 1.61-1.87 (m, 7H), 1.87-1.98 (m, 2H), 2.54-2.61 (m, 1H), 2.61-2.70 (m, 1H), 2.72-2.79 (m, 1H), 3.03-3.09 (m, 1H), 5.75 (s, 1H). HRMS Calculated for [C15H22F2N2O2+H]+: 301.1728. Found: 301.1751

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-ef03b72822024e2c84a9db6ca586aab6
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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