Hydrogen Bromide → HCID 66732459, compound

HRID 1963517Notes

Reaction equation

HRID 1963517 reaction equation
[F:1][CH:2]([F:19])[C@H:3]1[CH2:8][C@H:7]([C:9]2[O:13][NH:12][C:11](=[O:14])[CH:10]=2)[CH2:6][CH2:5][N:4]1C(OC)=O.Br>>[F:19][CH:2]([F:1])[C@H:3]1[CH2:8][C@H:7]([C:9]2[O:13][NH:12][C:11](=[O:14])[CH:10]=2)[CH2:6][CH2:5][NH:4]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730447HCID 131730447, compound

Product 1

HCID 66732459HCID 66732459, compoundYield 89.6%

Procedure

Trans-methyl 2-(difluoromethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (122 mg, 0.44 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 8.21 mL, 46.87 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo and the compound was purified by preparative HPLC on a XBridge C18 column (10 μm 250×19 ID mm) using a gradient of 0-10% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 19 mL/min. 5-(Trans-2-(difluoromethyl)piperidin-4-yl)isoxazol-3(2H)-one (86 mg, 89%) was isolated. 1H NMR (400 MHz, cd3od) δ 1.80-2.00 (m, 3H), 2.03-2.12 (m, 1H), 2.76-2.86 (m, 1H), 2.93-3.13 (m, 2H), 3.22-3.28 (m, 1H), 5.78 (s, 1H), 5.81 (dt, 1H). MS m/z 219 (M+H)+

Workup

  1. customThe solvent was removed in vacuo
  2. customthe compound was purified by preparative HPLC on a XBridge C18 column (10 μm 250×19 ID mm)
  3. custombuffer over 20 minutes

Sources & evidence

ORD record
ord-154cc3c38e3a4e3987fda23ac9e186f5
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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