Hydrogen Bromide → HCID 46937643, compound

HRID 1963521Notes

Reaction equation

HRID 1963521 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 66742254HCID 66742254, compound

Product 1

HCID 46937643HCID 46937643, compoundYield 64.2%

Procedure

(2S,4S)-Methyl 2-((4,4-difluorocyclohexyl)methyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (0.787 g, 2.20 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 17.31 mL, 98.82 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-((2S,4S)-2-((4,4-difluorocyclohexyl)methyl)-piperidin-4-yl)isoxazol-3(2H)-one (424 mg, 64%). 1H NMR (600 MHz, DMSO) δ 0.98-1.41 (m, 5H), 1.51-2.61 (m, 12H), 2.66-2.75 (m, 1H), 2.95-3.04 (m, 1H), 5.59-5.67 (m, 1H). HRMS Calculated for [C15H22F2N2O2+H]+: 301.1728. Found: 301.1713

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-4f6a5cdbb3f64742a8408bca807cedfd
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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