反应详情

(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.

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