Hydrogen Bromide → HCID 46938317, compound

HRID 1963407Notes

Reaction equation

HRID 1963407 reaction equation
[C:1]([C:5]1[S:9][C:8]([C@@H:10]2[CH2:15][C@H:14]([C:16]3[O:20][NH:19][C:18](=[O:21])[CH:17]=3)[CH2:13][CH2:12][N:11]2C(OC)=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Br>>[C:1]([C:5]1[S:9][C:8]([C@@H:10]2[CH2:15][C@H:14]([C:16]3[O:20][NH:19][C:18](=[O:21])[CH:17]=3)[CH2:13][CH2:12][NH:11]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66742114HCID 66742114, compound

Product 1

HCID 46938317HCID 46938317, compoundYield 16.65%

Procedure

(2S,4R)-Methyl 2-(5-tert-butylthiophen-2-yl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (50 mg, 0.14 mmol) (from example 42, step 3) was dissolved in hydrobromic acid (33% in AcOH, 1 mL, 6.08 mmol) and stirred at room temperature for 20 h. The solvent was evaporated in vacuo. The compound was purified by preparative HPLC on a XBridge C18 column (10 μm 250×19 ID mm) using a gradient of 10-50% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 25 minutes with a flow of 19 mL/min. 5-((2S,4R)-2-(5-tert-Butylthiophen-2-yl)piperidin-4-yl)isoxazol-3(2H)-one (7.00 mg, 16.65%) was isolated as a white solid. 1H NMR (600 MHz, cd3od) δ 1.36 (s, 9H), 2.03-2.12 (m, 1H), 2.12-2.19 (m, 1H), 2.26-2.33 (m, 1H), 2.40-2.46 (m, 1H), 3.09-3.17 (m, 1H), 3.18-3.24 (m, 1H), 3.34-3.40 (m, 1H), 4.38-4.44 (m, 1H), 5.75 (s, 1H), 6.78 (d, 1H), 6.96 (d, 1H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customThe compound was purified by preparative HPLC on a XBridge C18 column (10 μm 250×19 ID mm)
  3. custombuffer over 25 minutes

Sources & evidence

ORD record
ord-9a7db61860c54855bcdba76cf959081c
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…