Hydrogen Bromide → HCID 66735051, compound

HRID 1963505Notes

Reaction equation

HRID 1963505 reaction equation
[CH3:1][N:2]1[C:6]([C@H:7]2[CH2:12][C@@H:11]([C:13]3[O:17][NH:16][C:15](=[O:18])[CH:14]=3)[CH2:10][CH2:9][N:8]2C(OCC2C=CC=CC=2)=O)=[N:5][N:4]=[N:3]1.Br>>[CH3:1][N:2]1[C:6]([C@H:7]2[CH2:12][C@@H:11]([C:13]3[O:17][NH:16][C:15](=[O:18])[CH:14]=3)[CH2:10][CH2:9][NH:8]2)=[N:5][N:4]=[N:3]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66739232HCID 66739232, compound

Product 1

HCID 66735051HCID 66735051, compoundYield 67%

Procedure

(2R,4S)-Benzyl 2-(1-methyl-1H-tetrazol-5-yl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.231 g, 0.60 mmol) was dissolved in hydrogen bromide (33% in HOAc, 5.26 mL, 30.05 mmol) and allowed to react for 1 h. The mixture was evaporated and the residue was partitioned between water and EtOAc. The aqueous phase was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 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 100 mL/min. The compounds were detected by UV at 220 nm. Product fractions (which contained DMSO) were collected and the acetonitrile was evaporated. The aqueous phase was freeze dried. Most of the DMSO was left so the residue was dissolved in 2 mL of MeOH and loaded onto a 2 g SCX-2 column and the column washed with MeOH. The amine was liberated by running 10 mL of 10% triethylamine in MeOH through it. The solvent was evaporated and the residue was freeze dried from water to yield 5-((2R,4S)-2-(1-methyl-1H-tetrazol-5-yl)piperidin-4-yl)isoxazol-3(2H)-one (100 mg, 67%). 1H NMR (400 MHz, dmso) δ 1.47 (dq, 1H), 1.70-1.81 (m, 1H), 1.87 (d, 1H), 2.12 (d, 1H), 2.74 (dt, 1H), 2.92-3.02 (m, 1H), 3.04-3.13 (m, 1H), 4.09 (s, 3H), 4.18 (dd, 1H), 5.78 (s, 1H). HRMS Calcd for [(2×C10H14N6O2)+H]+: 501.2435. Found: 501.2418.

Workup

  1. customto react for 1 h
  2. customThe mixture was evaporated
  3. customthe residue was partitioned between water and EtOAc
  4. customThe aqueous phase was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm)
  5. custombuffer over 20 minutes
  6. customProduct fractions (which contained DMSO) were collected
  7. customthe acetonitrile was evaporated
  8. customdried
  9. waitMost of the DMSO was left so the residue
  10. dissolutionwas dissolved in 2 mL of MeOH
  11. washthe column washed with MeOH
  12. customThe solvent was evaporated
  13. dry with materialdried from water

Sources & evidence

ORD record
ord-2ea2f13136514b30b4cebfa1caaeca0d
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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