Hydrogen Bromide → HCID 66732176, compound

HRID 1963657Notes

Reaction equation

HRID 1963657 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH:25]=[C:26]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:27]=1)[CH2:8][C@@H:9]1[CH2:14][C@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][N:10]1C(OC)=O)([CH3:4])([CH3:3])[CH3:2].Br>>[C:28]([C:26]1[CH:25]=[C:7]([CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:27]=1)[CH2:8][C@@H:9]1[CH2:14][C@H:13]([C:15]2[O:19][NH:18][C:17](=[O:20])[CH:16]=2)[CH2:12][CH2:11][NH:10]1)([CH3:30])([CH3:31])[CH3:29]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732566HCID 66732566, compound

Product 1

HCID 66732176HCID 66732176, compoundYield 61.8%

Procedure

(2S,4R)-Methyl 2-(3,5-di-tert-butylbenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (619 mg, 1.44 mmol) (from example 146, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 10 mL, 57.10 mmol) and the mixture stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx III, 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,4R)-2-(3,5-di-tert-butylbenzyl)piperidin-4-yl)isoxazol-3(2H)-one (330 mg, 61%). 1H NMR (600 MHz, cd3od) δ 1.30 (s, 18H), 1.63 (q, 1H), 1.80 (dq, 1H), 2.19-2.27 (m, 2H), 2.86-3.18 (m, 4H), 3.43-3.56 (m, 2H), 5.73 (s, 1H), 7.10 (d, 2H), 7.37-7.40 (m, 1H). HRMS Calculated for [C23H34N2O2+H]+: 371.2698. Found: 371.2693

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by preparative HPLC (Instrument: FractionLynx III, 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-732351020c1a4fa79c4ebd96b0a7fcfd
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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