반응 #80998

ord-f99893ef76934bd0ade29077520f3f05

반응 조건

온도
-40°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도was heated
  2. 2
    온도to cool
  3. 3
    기타the solvent was removed in vacuo
  4. 4
    기타to give an oil which
  5. 5
    온도to warm to -20° C. over the next 0.5 hr
  6. 6
    기타After removal of the solvent in vacuo
  7. 7
    세척washed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL)
  8. 8
    기타dried over Na2So4
  9. 9
    농축concentrated in vacuo
  10. 10
    기타afforded

실험 절차

A mixture of 1.54 g (5.41 mmol) of (2S,3S,5S)-2,5-diamino-1,6-diphenyl-3-hydroxyhexane and 0.673 g (5.41 mmol) of phenylboric acid in anhydrous toluene (130 mL) was heated at reflux under argon for 2 hrs with removal of H2O by a Dean-Slark trap. The resulting yellow solution was allowed to cool and the solvent was removed in vacuo to give an oil which solidified upon standing. The residue was taken up in 90 ml of THF, cooled to -40° C., and treated dropwise under Ar atmosphere over a period of 1 h with 1.11 g (3.78 mmol) of ((5-isoxazolyl)methyl)-(4-nitrophenyl)carbonate in 40 ml of THF. The solution was allowed to warm to -20° C. over the next 0.5 hr, then was stirred at 0° C. for 2.5 hrs and at room temperature for 1 hr. After removal of the solvent in vacuo, the residue was taken up in ethyl acetate (200 mL), washed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL), dried over Na2So4 and concentrated in vacuo. Silica gel chromatography of the residue using a gradient of methanol in chloroform (2%, 4%, 6%) afforded a mixture of the desired product and its regioisomer. Purification of the mixture on two consecutive 250 g SiO2 columns (deactivated with 1% isopropylamine/CH2Cl2) with a gradient of isopropylamine/CH2Cl2 (0.5%, 1%) afforded the desired compound as a sticky solid (0.730 g, 1.78 mmol, 33%): 1H NMR (DMSO-d6) δ1.17-1.57 (m, 5H), 2.56-2.69 (m, 2H), 2.75-2.86 (m, 1H), 2.89-3.00 (m, 2H), 3.53-3.71 (m, 3H), 5.06 (s, 2H), 6.32 (d, J=2.4 Hz, 1H), 7.11-7.30 (m, 10H), 8.54 (d, J=2.4 Hz, 1H). Mass spectrum: (M+H)+ =410.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US05616720uspto-grants-1997_04