Hydrogen Bromide → HCID 46937641, compound

HRID 1963515Notes

Reaction equation

HRID 1963515 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 68505101HCID 68505101, compound

Product 1

HCID 46937641HCID 46937641, compoundYield 101.6%

Procedure

(2R,4S)-Methyl 2-(difluoromethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (278 mg, 1.01 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 7.93 mL, 45.29 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-((2R,4S)-2-(Difluoromethyl)piperidin-4-yl)isoxazol-3(2H)-one (224 mg) was isolated. 1H NMR (400 MHz, cd3od) δ 1.66-1.77 (m, 1H), 1.77-1.89 (m, 1H), 2.24-2.31 (m, 1H), 2.36-2.43 (m, 1H), 3.12-3.27 (m, 2H), 3.51-3.58 (m, 1H), 3.73-3.86 (m, 1H), 5.84 (s, 1H), 6.14 (dt, 1H). HRMS Calcd for [C9H12F2N2O2+H]+: 219.0945. Found: 219.0950.

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-0a49cc5a89a2488093a7b8625a7bf3a7
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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